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University of Georgia
1.
Gregg, Laura.
Group I metabotropic glutamate receptors modulate endocannabinoid-mediated stress-induced analgesia.
Degree: 2014, University of Georgia
URL: http://hdl.handle.net/10724/24617
► Stress-induced analgesia (SIA) is mediated by mobilization of endocannabinoid lipids such as 2-arachidonoylglycerol (2-AG) in the midbrain periaqueductal gray (PAG). 2-AG may be synthesized on…
(more)
▼ Stress-induced analgesia (SIA) is mediated by mobilization of endocannabinoid lipids such as 2-arachidonoylglycerol (2-AG) in the midbrain periaqueductal gray (PAG). 2-AG may be synthesized on demand to induce SIA through the consecutive
activation of two enzymes- phospholipase C (PLC) and diacylglycerol lipase (DGL). We examined whether activation of postsynaptic group I metabotropic glutamate receptors (mGluRs) would enhance SIA because of their known coupling to PLC. Microinjection of
the group I mGluR agonist DHPG into the dorsolateral PAG (dPAG) enhanced SIA through a CB1-dependent mechanism. Microinjection of the DGL inhibitors tetrahydrolipstatin (THL) and RHC80267 into the dPAG suppressed SIA. The DHPG-induced enhancement of SIA
was blocked by THL. Off-site injections of the active compounds did not alter SIA. Our results support the hypothesis that exposure to environmental stressors stimulates synthesis of 2-AG through the PLC/DGL pathway to induce SIA. Moreover, this process
may be initiated by activation of group I mGluRs.
Subjects/Keywords: endocannabinoid; antinociception; metabotropic glutamate receptors
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APA (6th Edition):
Gregg, L. (2014). Group I metabotropic glutamate receptors modulate endocannabinoid-mediated stress-induced analgesia. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/24617
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Gregg, Laura. “Group I metabotropic glutamate receptors modulate endocannabinoid-mediated stress-induced analgesia.” 2014. Thesis, University of Georgia. Accessed February 28, 2021.
http://hdl.handle.net/10724/24617.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Gregg, Laura. “Group I metabotropic glutamate receptors modulate endocannabinoid-mediated stress-induced analgesia.” 2014. Web. 28 Feb 2021.
Vancouver:
Gregg L. Group I metabotropic glutamate receptors modulate endocannabinoid-mediated stress-induced analgesia. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Feb 28].
Available from: http://hdl.handle.net/10724/24617.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Gregg L. Group I metabotropic glutamate receptors modulate endocannabinoid-mediated stress-induced analgesia. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/24617
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Georgia
2.
Gregg, Laura Corrine.
Activation of group III metabotropic glutamate receptors regulates stress-induced analgesia through an endocannabinoid mechanism.
Degree: 2014, University of Georgia
URL: http://hdl.handle.net/10724/26333
► The endocannabinoid 2-arachidonoylglycerol (2-AG) produces adaptive changes in pain responses following exposure to environmental stressors. This phenomenon, termed stress-induced analgesia (SIA), is dependent upon mobilization…
(more)
▼ The endocannabinoid 2-arachidonoylglycerol (2-AG) produces adaptive changes in pain responses following exposure to environmental stressors. This phenomenon, termed stress-induced analgesia (SIA), is dependent upon mobilization and
accumulation of 2-AG in the periaqueductal gray (PAG). 2-AG within the PAG may activate CB1 receptors on GABAergic neurons to reduce inhibition of output neurons that form part of a descending antinociceptive pathway. Alternatively, 2-AG may activate CB1
receptors on glutamatergic neurons to inhibit pro-nociceptive pathways that facilitate pain. 2-AG acts as a retrograde signal that binds to CB1 receptors to produce antinociception. However, the mechanisms contributing to the mobilization of 2-AG are
only beginning to be discovered. We examined the role of presynaptic group III metabotropic glutamate receptors (mGluRs), which are negatively coupled to adenylyl cyclase and reduce GABAergic inhibition, on the phenomenon of SIA in the PAG.
Microinjection into the dorsolateral PAG (dlPAG) of the group III mGluR agonst L-AP4 produced a dose-dependent enhancement of SIA through a CB1-dependent mechanism. By contrast, off-site injections of L-AP4 failed to enhance SIA. The L-AP4-induced
enhancement of SIA was blocked by the group III mGluR antagonist UBP1112 at a dose that was found to be ineffective in modulating SIA when administered alone. Microinjection of the group III mGluR antagonist UBP1112 into the dlPAG produced a
dose-dependent suppression of SIA and also blocked the enhancement of SIA induced by L-AP4. This effect involved the dorsolateral PAG because off-site injections failed to alter SIA. Our findings suggest a previously unrecognized role for group III
mGluRs in controlling endocannabinoid-dependent stress-induced analgesia, presumably by controlling the mobilization of endocannabinoids, likely 2-AG, in the PAG.
Subjects/Keywords: endocannabinoid; antinociception; metabotropic glutamate receptor
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Gregg, L. C. (2014). Activation of group III metabotropic glutamate receptors regulates stress-induced analgesia through an endocannabinoid mechanism. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/26333
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Gregg, Laura Corrine. “Activation of group III metabotropic glutamate receptors regulates stress-induced analgesia through an endocannabinoid mechanism.” 2014. Thesis, University of Georgia. Accessed February 28, 2021.
http://hdl.handle.net/10724/26333.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Gregg, Laura Corrine. “Activation of group III metabotropic glutamate receptors regulates stress-induced analgesia through an endocannabinoid mechanism.” 2014. Web. 28 Feb 2021.
Vancouver:
Gregg LC. Activation of group III metabotropic glutamate receptors regulates stress-induced analgesia through an endocannabinoid mechanism. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Feb 28].
Available from: http://hdl.handle.net/10724/26333.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Gregg LC. Activation of group III metabotropic glutamate receptors regulates stress-induced analgesia through an endocannabinoid mechanism. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/26333
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
3.
Andrà Luiz dos Reis Barbosa.
Colite experimental induzida pelo Ãcido trinitrobenzeno sulfÃnico (TNBS) em ratos reduz a resposta hipernociceptiva inflamatÃria- papel das vias endocanabinÃides, opiÃides endÃgenos e NO/GMPC/PKG/K+ATP.
Degree: PhD, 2011, Universidade Federal do Ceará
URL: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=6177
;
► O presente teve por objetivo avaliar a diminuiÃÃo da resposta hipernociceptiva inflamatÃria no curso do desenvolvimento da colite experimental induzida pelo Ãcido TNBS em ratos,…
(more)
▼ O presente teve por objetivo avaliar a diminuiÃÃo da resposta hipernociceptiva inflamatÃria no curso do desenvolvimento da colite experimental induzida pelo Ãcido TNBS em ratos, bem como avaliar o papel da via NO/GMPc/PKG/K+ATP e a participaÃÃo de opioides endÃgenos e endocanabinoides neste evento. Para tanto, as colites foram induzidas por TNBS (20mg) diluÃdo em etanol a 50% ou etanol a 50%. O grupo controle recebeu somente salina via transanal. TrÃs ou quatorze dias apÃs a induÃÃo das colites foram avaliados os seguintes parÃmetros: edema de pata por carragenina (Cg; 500μg/pata direita) ou dextrana (Dxt; 500μg/pata direita.) por pletismometria, atividade da enzima mieloperoxidase (MPO), migraÃÃo de neutrÃfilos para cavidade pleural induzidas por Cg (500μg/pata direita) e a hipernocicepÃÃo mecÃnica induzida por PGE2 (100ng/pata) ou Cg (500μg/pata) aferido por analgesÃmetro digital (InsightÂ). Para verificar a participaÃÃo da via NO/GMPc/PKG/K+ATP na diminuiÃÃo da resposta hipernocicetiva da colite induzida por TNBS foram usados o L-Noarg (antagonista da NOSi; 100ng/pata) , O ODQ (bloqueador da guanilato ciclase soluivel; 8μg/pata), o KT5823 (antagonista da PKG; 1,5 μg/pata) e a glibenclamida (bloqueadora dos canais de K+ATP; 160μg/pata). Depois, para avaliar a participaÃÃo opiÃide e canabinÃide nesse evento, naloxona (antagonista de receptor opioide, 1,0 μg/pata) ou AM251 (antagonista de receptor canabinoide ; 1, 80 μg/pata) ou AM630 (antagonista de receptor canabinoide tipo 2; 25 μg/pata) foram injetados respectivamente. Os animais com colite induzida por TNBS apresentaram uma inibiÃÃo significativa do edema de pata tanto com o Cg (TrÃs ou quatorze dias apÃs a induÃÃo) quanto com Dxt (TrÃs dias apÃs a induÃÃo), quando comparados com os outros grupos em estudo. Em nenhum dos dias estudados, foram observadas diferenÃas na atividade da MPO na pata e nem na avaliaÃÃo da migraÃÃo de neutrÃfilos para a cavidade pleural induzidas por Cg. Ratos com colite induzida por TNBS apresentavam diminuiÃÃo na resposta hipernociceptiva induzida por Cg e PGE2. O tratamento com o ODQ, KT5823 e glibenclamida, naloxona, AM251 e AM630 reverteram esse efeito. O L-Noarg tambÃm reverteu o efeito entinociceptivo da colite induzida por TNBS, mas com a administraÃÃo da L-Arginina esse efeito foi recuperado. Apartir dos nossos resultados podemos concluir que a colite induzida por TNBS diminuiu a hipernocicepÃÃo inflamatÃria induzida tanto por carragenina quanto por PGE2 por dimimuir parÃmetros inflamatÃrios agudos como a resposta edematogÃnica a estÃmulos inflamatÃrios. AlÃm disso, esse efeito antinociceptivo parece ser independente da infiltraÃÃo de neutrÃfilos, mas dependente da ativaÃÃo da via final NO/GMPc/PKG/K+ATP e estimulada pelas aÃÃes dos opiÃides e canabinÃides endÃgenos.
The aim of this study was to investigate a possible involvement of the opioids, endocannabinoids and NO/cGMP/PKG/K+ATP pathway in the antinociception of the CrohnÂs experimental model in hypernociception…
Advisors/Committee Members: Marcellus Henrique Loiola Ponte de Souza, Mariana Lima Vale, Ana Maria Sampaio Assereuy, Waldiceu Aparecido Verri JÃnior, Aytan Miranda Sipahi.
Subjects/Keywords: FARMACOLOGIA; AntinocicepÃÃo; InflamaÃÃo; Colitis; Antinociception; Inflammation; Colite
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APA ·
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APA (6th Edition):
Barbosa, A. L. d. R. (2011). Colite experimental induzida pelo Ãcido trinitrobenzeno sulfÃnico (TNBS) em ratos reduz a resposta hipernociceptiva inflamatÃria- papel das vias endocanabinÃides, opiÃides endÃgenos e NO/GMPC/PKG/K+ATP. (Doctoral Dissertation). Universidade Federal do Ceará. Retrieved from http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=6177 ;
Chicago Manual of Style (16th Edition):
Barbosa, Andrà Luiz dos Reis. “Colite experimental induzida pelo Ãcido trinitrobenzeno sulfÃnico (TNBS) em ratos reduz a resposta hipernociceptiva inflamatÃria- papel das vias endocanabinÃides, opiÃides endÃgenos e NO/GMPC/PKG/K+ATP.” 2011. Doctoral Dissertation, Universidade Federal do Ceará. Accessed February 28, 2021.
http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=6177 ;.
MLA Handbook (7th Edition):
Barbosa, Andrà Luiz dos Reis. “Colite experimental induzida pelo Ãcido trinitrobenzeno sulfÃnico (TNBS) em ratos reduz a resposta hipernociceptiva inflamatÃria- papel das vias endocanabinÃides, opiÃides endÃgenos e NO/GMPC/PKG/K+ATP.” 2011. Web. 28 Feb 2021.
Vancouver:
Barbosa ALdR. Colite experimental induzida pelo Ãcido trinitrobenzeno sulfÃnico (TNBS) em ratos reduz a resposta hipernociceptiva inflamatÃria- papel das vias endocanabinÃides, opiÃides endÃgenos e NO/GMPC/PKG/K+ATP. [Internet] [Doctoral dissertation]. Universidade Federal do Ceará 2011. [cited 2021 Feb 28].
Available from: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=6177 ;.
Council of Science Editors:
Barbosa ALdR. Colite experimental induzida pelo Ãcido trinitrobenzeno sulfÃnico (TNBS) em ratos reduz a resposta hipernociceptiva inflamatÃria- papel das vias endocanabinÃides, opiÃides endÃgenos e NO/GMPC/PKG/K+ATP. [Doctoral Dissertation]. Universidade Federal do Ceará 2011. Available from: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=6177 ;

Texas A&M University
4.
Puga, Denise Alejandra.
Pain Processing in the Isolated Spinal Cord: Adaptive Nociceptive Modifications.
Degree: PhD, Psychology, 2012, Texas A&M University
URL: http://hdl.handle.net/1969.1/ETD-TAMU-2011-05-9149
► We utilize a simple instrumental (response-outcome) learning task to measure spinal plasticity in the isolated spinal cord. Peripheral uncontrollable nociceptive input has been shown to…
(more)
▼ We utilize a simple instrumental (response-outcome) learning task to measure
spinal plasticity in the isolated spinal cord. Peripheral uncontrollable nociceptive input
has been shown to disrupt spinal instrumental learning and induce enhance tactile
reactivity. In contrast, 1.5mA of continuous shock has been found to induce
antinociception and protect spinal plasticity from the detrimental consequences of
uncontrollable stimulation. The experiments of this dissertation examined the link
between the beneficial effects of continuous stimulation and
antinociception.
The results replicated previous work examining the protective and
antinociceptive effect of 1.5mA of continuous shock (Experiments 1-2). Novel to this
research was the inclusion of a lower (0.5mA) intensity continuous stimulation. Results
revealed that 0.5mA of continuous shock induced a comparable
antinociception to that
seen with 1.5mA of continuous shock (Experiment 1). At this lower intensity, however,
continuous shock was unable to protect the isolated spinal cord from the detrimental
effect of intermittent stimulation (Experiment 2). Further examination revealed that co-administration of intermittent and continuous shock did not affect continuous shockinduced
antinociception. This was true at both the higher (1.5mA) and lower (0.5mA)
intensities of continuous shock (Experiment 3).
When 0.5mA of continuous shock was administered prior to intermittent shock,
this intensity of continuous shock was better able to immunize the spinal cord from the
induction of the learning deficit than 1.5mA (Experiment 4). Further analysis called into
question the link between
antinociception and the protective effect of continuous shock,
as the beneficial effect of continuous shock outlasted the expression of
antinociception
(Experiment 5). Moreover, 0.5mA of continuous shock was found to reverse the
expression of the learning deficit, when continuous stimulation was given after
intermittent shock treatment (Experiment 6).
While blocking the induction of
antinociception was not sufficient to prevent the
immunizing effect of continuous shock, data suggest that the mu opioid receptor is
implicated in the beneficial impact of continuous stimulation (Experiments 7 and 8).
Endogenous brain derived neurotrophic factor (BDNF) release was also found to play a
role (Experiment 9). Moreover, continuous shock was found to down-regulate the
expression of early genes implicated in the development of central sensitization, c-fos
and c-jun. Finally, we found that while continuous stimulation was detrimental to
locomotor recovery after spinal cord injury, the combined treatment of continuous and
intermittent shock did not negatively affect recovery (Experiments 11 and 12).
Advisors/Committee Members: Grau, James W. (advisor), Meagher, Mary (committee member), Miranda, Rajesh (committee member), Hook, Michelle (committee member).
Subjects/Keywords: Spinal cord; plasticity; spinal learning; antinociception
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Puga, D. A. (2012). Pain Processing in the Isolated Spinal Cord: Adaptive Nociceptive Modifications. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-2011-05-9149
Chicago Manual of Style (16th Edition):
Puga, Denise Alejandra. “Pain Processing in the Isolated Spinal Cord: Adaptive Nociceptive Modifications.” 2012. Doctoral Dissertation, Texas A&M University. Accessed February 28, 2021.
http://hdl.handle.net/1969.1/ETD-TAMU-2011-05-9149.
MLA Handbook (7th Edition):
Puga, Denise Alejandra. “Pain Processing in the Isolated Spinal Cord: Adaptive Nociceptive Modifications.” 2012. Web. 28 Feb 2021.
Vancouver:
Puga DA. Pain Processing in the Isolated Spinal Cord: Adaptive Nociceptive Modifications. [Internet] [Doctoral dissertation]. Texas A&M University; 2012. [cited 2021 Feb 28].
Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2011-05-9149.
Council of Science Editors:
Puga DA. Pain Processing in the Isolated Spinal Cord: Adaptive Nociceptive Modifications. [Doctoral Dissertation]. Texas A&M University; 2012. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2011-05-9149

University of Nairobi
5.
Kariuki, Hellen Nyambura.
Antinociceptive activities of extracts from selected medicinal plants using animal models
.
Degree: 2013, University of Nairobi
URL: http://hdl.handle.net/11295/62657
► This study reports the findings of the scientific evaluation of selected indigenous plants used by Kenyan communities for the management of pain and painful conditions.…
(more)
▼ This study reports the findings of the scientific evaluation of selected indigenous plants used by Kenyan communities for the management of pain and painful conditions.
Pain is associated with high morbidity and socioeconomic burden. It is the key symptom for the diagnosis of several disease conditions and is widely accepted as one of the most
important determinants of quality of life.
Plants have been claimed to have analgesic or antinociceptive effects by several communities in East Africa and a great number of people use plants for management of painful conditions. Nine plants namely, Toddalia asiatica, Senna singueana, Rhus natalensis, Teclea simplicifolia, Clausena anisata, Warburgia ugandensis, Sapium ellipticum, Albizia anthelmintica and Psiadia punctulata were assessed for antinociceptive properties using standard nociception animal models that target thermal and chemical stimuli. All the test mice used in the study were initially assessed for quality neurological and motor function. The selected mice were used to assess the sensorimotor effects of the nine plants at dose 200 and 100 mg I kg. Albizia anthelmintica and Psiadia punctulata induced impaired motor coordination in mice at the tested doses and therefore were disqualified for further investigations. Assessment of the central nociception effects of the remaining seven plants using the tail flick test, confirmed signi ficant antinociceptive effects of root extracts of Toddalia asiatica (p < 0.001), Senna singueana (p < 0.05) and Rhus natalensis ( p < 0.01 )at dose 200mg I kg. Only T.asiatica exhibited significant (p < 0.01) effect at lQOmgI kg dose compared to the negative controls.
Further tests using the hot plate assay (thermal stimuli) and the acetic acid induced writhing test (chemical stimuli) confirmed T. asiatica root extract as having superior anti nociceptive affects compared to the other plants. T. asiatica was also found to have antinociceptive effects in pain caused by inflammatory chemicals using the formalin test.
Isolation of compounds from the root extract of T. asiatica yielded seven compounds, four
alkaloids and three coumarins that were further characterized by NMR. The coumarins,
Isopimpinellin and 6-(3-methylbut-2enyloxy)-8-methoxy2h-chromen-2-one did not induce
any significant antinociceptive activity in the tail flick assay while 6, 7-dimethoxy-5- (3methyl-2-oxobutyl)-2H-chromen-2-one, 8-Acetonyldihydrochelerythrine and 6-(2, 3dihydroxy-3-methylbutyl)-5,7-dimethoxy-2H-chromen-2-one)
induced significant (p < 0.05) antinociceptive effect compared to the negative controls. The alkaloids, 8-oxochelerythrine and dihydrochlerythrine exhibited significant (p < 0.001) antinociceptive effects with dihydrochlerythrine showing the highest activity.
Dihydrochlerythrine was isolated from the root extract of T. asiatica and assayed for
antinociception for the first time in this study. More antinociceptive tests need to be done to ascertain the antinociceptive activities in chronic pain models as well comparative studies with…
Subjects/Keywords: Antinociception;
Toddalia asiatica;
Mice;
Alkaloid;
dihydrochlerythrine
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kariuki, H. N. (2013). Antinociceptive activities of extracts from selected medicinal plants using animal models
. (Thesis). University of Nairobi. Retrieved from http://hdl.handle.net/11295/62657
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Kariuki, Hellen Nyambura. “Antinociceptive activities of extracts from selected medicinal plants using animal models
.” 2013. Thesis, University of Nairobi. Accessed February 28, 2021.
http://hdl.handle.net/11295/62657.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kariuki, Hellen Nyambura. “Antinociceptive activities of extracts from selected medicinal plants using animal models
.” 2013. Web. 28 Feb 2021.
Vancouver:
Kariuki HN. Antinociceptive activities of extracts from selected medicinal plants using animal models
. [Internet] [Thesis]. University of Nairobi; 2013. [cited 2021 Feb 28].
Available from: http://hdl.handle.net/11295/62657.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kariuki HN. Antinociceptive activities of extracts from selected medicinal plants using animal models
. [Thesis]. University of Nairobi; 2013. Available from: http://hdl.handle.net/11295/62657
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
6.
Gonçalves, Tânia Cristina.
Evaluation multi-échelle de toxines de venins comme agents antinociceptifs potentiels : Multiscale evaluation of venom toxins as potential antinociceptive agents.
Degree: Docteur es, Sciences pharmacologiques, 2018, Université Paris-Saclay (ComUE)
URL: http://www.theses.fr/2018SACLS587
► L’objectif de ma thèse était d’identifier, comme agents antinociceptifs potentiels, des toxines de venins originales par leur séquence et/ou leur provenance. Dans cette optique, un…
(more)
▼ L’objectif de ma thèse était d’identifier, comme agents antinociceptifs potentiels, des toxines de venins originales par leur séquence et/ou leur provenance. Dans cette optique, un criblage à haut débit de deux banques de venins a été réalisé par des méthodes électrophysiologiques de "patch-clamp" automatique, sur des lignées cellulaires exprimant le sous-type neuronal hNaV1.7 de canaux sodium (versus celles exprimant le sous-type cardiaque hNaV1.5), une cible antidouleur validée génétiquement et fortement exprimée au niveau des neurones sensoriels primaires des ganglions de la racine dorsale, premier support de la transmission du message nociceptif.Le criblage de la première banque de venins (appartenant à Smartox Biotechnology) a permis l’identification et la caractérisation, par des approches structurales et fonctionnelles multi-échelles (de la cellule in vitro à l’organisme in vivo), de 2 peptides de venins d’araignées ayant des propriétés potentiellement antinociceptives : (1) la cyriotoxine-1a du venin de Cyriopagopus schioedtei, dont les propriétés fonctionnelles sont proches de celles des peptides appartenant à la famille 1 des toxines d’araignées inhibant les canaux sodium, et (2) la poecitoxine-1a du venin de Poecilotheria subfusca, qui présente une meilleure affinité pour le sous-type hCaV1.2 de canaux calcium que pour le sous-type hNaV1.7. Nous avons également mené une étude de "structure-activité" afin d’améliorer le profil de sélectivité de la phlotoxine-1 d’une araignée Phlogiellus, connue pour son activité antinocieptive. Finalement, nous avons mis en évidence une interaction directe entre l’huwentoxine-IV, déjà connue comme agent antinociceptif potentiel, et le sous-type neuronal NaV1.6, responsable d’effets neuromusculaires indésirables. Le criblage de la deuxième banque de venins (appartenant à SANOFI) a permis d’identifier des hits intéressants provenant de venins d’araignées et de scorpions non étudiés jusqu’à présent et ayant une séquence originale présentant peu d’homologie avec les séquences déjà connues.
The aim of my thesis was to identify original venom toxins, by their sequence and/or origin, as potential antinociceptive agents. In this context, a high-throughput screening of two venom libraries was performed, by automated patch-clamp electrophysiology, on cell lines expressing the hNaV1.7 neuronal subtype of sodium channels (versus those expressing the hNaV1.5 cardiac subtype), a genetically-validated and strongly expressed pain target in the primary sensory neurons of dorsal root ganglia, the first support of nociceptive message transmission.The screening of the first venom library (belonging to Smartox Biotechnology) allowed the identification and characterization, by structural and multiscale functional approaches (from the cell in vitro to the organism in vivo), of 2 peptides from spider venoms having potential antinociceptive properties : (1) cyriotoxin-1a from Cyriopagopus schioedtei venom, whose functional properties are close to those of peptides belonging to family 1 of spider…
Advisors/Committee Members: Servent, Denis (thesis director).
Subjects/Keywords: Toxines de venins; Antinociception; Canaux sodium dépendants du potentiel; Electrophysiologie; Venom toxins; Antinociception; Voltage-Dependant sodium channels; Electrophysiology
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Gonçalves, T. C. (2018). Evaluation multi-échelle de toxines de venins comme agents antinociceptifs potentiels : Multiscale evaluation of venom toxins as potential antinociceptive agents. (Doctoral Dissertation). Université Paris-Saclay (ComUE). Retrieved from http://www.theses.fr/2018SACLS587
Chicago Manual of Style (16th Edition):
Gonçalves, Tânia Cristina. “Evaluation multi-échelle de toxines de venins comme agents antinociceptifs potentiels : Multiscale evaluation of venom toxins as potential antinociceptive agents.” 2018. Doctoral Dissertation, Université Paris-Saclay (ComUE). Accessed February 28, 2021.
http://www.theses.fr/2018SACLS587.
MLA Handbook (7th Edition):
Gonçalves, Tânia Cristina. “Evaluation multi-échelle de toxines de venins comme agents antinociceptifs potentiels : Multiscale evaluation of venom toxins as potential antinociceptive agents.” 2018. Web. 28 Feb 2021.
Vancouver:
Gonçalves TC. Evaluation multi-échelle de toxines de venins comme agents antinociceptifs potentiels : Multiscale evaluation of venom toxins as potential antinociceptive agents. [Internet] [Doctoral dissertation]. Université Paris-Saclay (ComUE); 2018. [cited 2021 Feb 28].
Available from: http://www.theses.fr/2018SACLS587.
Council of Science Editors:
Gonçalves TC. Evaluation multi-échelle de toxines de venins comme agents antinociceptifs potentiels : Multiscale evaluation of venom toxins as potential antinociceptive agents. [Doctoral Dissertation]. Université Paris-Saclay (ComUE); 2018. Available from: http://www.theses.fr/2018SACLS587
7.
Luana Maria Castelo Melo Silva.
Atividades antinociceptiva e antiinflamatÃria da lectina da alga marinha vermelha Pterocladiella capilacea (S.G. Gmelin) Santelices & Hommersand
.
Degree: Master, 2008, Universidade Federal do Ceará
URL: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=2313
;
► Lectinas de algas marinhas tÃm-se mostrado importantes ferramentas biotecnolÃgicas. Objetivou-se estudar as atividades antinociceptivas e antiinflamatÃrias da lectina da alga marinha vermelha Pterocladiella capillacea (Pc).…
(more)
▼ Lectinas de algas marinhas tÃm-se mostrado importantes ferramentas biotecnolÃgicas. Objetivou-se estudar as atividades antinociceptivas e antiinflamatÃrias da lectina da alga marinha vermelha Pterocladiella capillacea (Pc). A Pc, apresentando atividade hemaglutinante contra eritrÃcitos tripsinizados de coelho, foi obtida a partir da aplicaÃÃo do extrato protÃico total em cromatografia de troca iÃnica em coluna de DEAE-celulose seguida da cromatografia de afinidade em coluna de goma de guar. A seguir, foi utilizada nos ensaios de nocicepÃÃo e inflamaÃÃo, utilizando camundongos machos Swiss e ratos machos Wistar, respectivamente. Pc (0,9; 8,1 ou 72,9 mg/kg; i.v) foi administrada 30 min antes de cada estÃmulo nocigÃnico, ou seja, antes da injeÃÃo i.p de Ãcido acÃtico a 0,8% (10 μL/mL), da injeÃÃo intraplantar de formalina a 1% (20 μL/pata) ou do teste da Placa quente (51Â1 ÂC), e comparada a animais nÃo tratados ou prÃ-tratados com Indometacina ou Morfina, ambas a 5 mg/kg; s.c. Observou-se que a Pc (0,9; 8,1 ou 72,9 mg/kg) reduziu significantemente o nÃmero de contorÃÃes abdominais induzidas pelo Ãcido acÃtico em 29,2%; 39,3%, e 51,9%, respectivamente. Pc (72,9 mg/kg) tambÃm reduziu (p<0,05) a fase 1 (neurogÃnica) e a fase 2 (inflamatÃria) observadas apÃs administraÃÃo da formalina, em 58% e 87%, respectivamente. Entretanto, a Pc (72,9 mg/kg) nÃo foi capaz de reduzir a nocicepÃÃo observada no teste da Placa Quente, quando comparada à morfina. Os efeitos antinociceptivos da Pc foram abolidos quando a Pc foi prÃ-incubada com a glicoproteÃna mucina (1,25 mg/mL), inibidora de sua atividade hemaglutinante. Sugere-se, portanto, que a atividade antinociceptiva da Pc possa ser predominante via inibiÃÃo de mecanismos perifÃricos. Assim, seguiram-se os ensaios de induÃÃo da migraÃÃo neutrofÃlica para cavidade peritoneal ou do edema de pata de ratos por Carragenana (Cg-tipo l; 500 g/cavidade ou pata), onde observou-se que a administraÃÃo da Pc (8,1 mg/kg; i.v) 30 min antes da Cg reduziu significativamente a contagem do nÃmero de neutrÃfilos em 84%. No entanto, a Pc nÃo foi capaz de prevenir o edema de pata induzido pela Cg. Desta forma, sugere-se que esta proteÃna foi capaz de reduzir o mecanismo de migraÃÃo de neutrÃfilos, possivelmente ligando-se à molÃculas especÃficas celulares, como por exemplo, selectinas. Para confirmar sua seguranÃa, a PC (8,1 mg/kg) foi administrada em camundongos diariamente e no 7 dia foram coletadas amostras sanguÃneas para dosagens de urÃia e transaminases (TGO e TGP), e pesados rins e fÃgado. Observou-se que a Pc nÃo causou alteraÃÃes significativas, sugerindo portanto, ser segura no perÃodo de administraÃÃo avaliado. Dessa forma, considerando os dados em conjunto, conclui-se que a Pc possui propriedades antinociceptiva e antiinflamatÃria com aÃÃo perifÃrica.
Marine algae lectins had been showing important biotechnical tools. Our objectives were to study the antinociceptive and anti-inflammatory activities of the lectin from the marine red alga Pterocladiella capillacea (Pc). The Pc,…
Advisors/Committee Members: Vilma de Lima, Norma Maria Barros Benevides, Maria GonÃalves Pereira.
Subjects/Keywords: BIOQUIMICA; Lectina; Alga marinha; AntinocicepÃÃo; InflamaÃÃo; Lectin; Marine algae; Antinociception; Inflammation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Silva, L. M. C. M. (2008). Atividades antinociceptiva e antiinflamatÃria da lectina da alga marinha vermelha Pterocladiella capilacea (S.G. Gmelin) Santelices & Hommersand
. (Masters Thesis). Universidade Federal do Ceará. Retrieved from http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=2313 ;
Chicago Manual of Style (16th Edition):
Silva, Luana Maria Castelo Melo. “Atividades antinociceptiva e antiinflamatÃria da lectina da alga marinha vermelha Pterocladiella capilacea (S.G. Gmelin) Santelices & Hommersand
.” 2008. Masters Thesis, Universidade Federal do Ceará. Accessed February 28, 2021.
http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=2313 ;.
MLA Handbook (7th Edition):
Silva, Luana Maria Castelo Melo. “Atividades antinociceptiva e antiinflamatÃria da lectina da alga marinha vermelha Pterocladiella capilacea (S.G. Gmelin) Santelices & Hommersand
.” 2008. Web. 28 Feb 2021.
Vancouver:
Silva LMCM. Atividades antinociceptiva e antiinflamatÃria da lectina da alga marinha vermelha Pterocladiella capilacea (S.G. Gmelin) Santelices & Hommersand
. [Internet] [Masters thesis]. Universidade Federal do Ceará 2008. [cited 2021 Feb 28].
Available from: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=2313 ;.
Council of Science Editors:
Silva LMCM. Atividades antinociceptiva e antiinflamatÃria da lectina da alga marinha vermelha Pterocladiella capilacea (S.G. Gmelin) Santelices & Hommersand
. [Masters Thesis]. Universidade Federal do Ceará 2008. Available from: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=2313 ;
8.
Márcia Alair da Silva Pereira.
ESTUDO DA ATIVIDADE ANTINOCICEPTIVA DA ADENOSINA EM CAMUNDONGOS - ANÁLISE DO MECANISMO DE AÇÃO.
Degree: 2005, Universidade do Vale do Itajaí
URL: http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=104
► Adenosine and adenosine 5-trifosphate (ATP) exerts a modulatory role in inflammatory response and pain transmission. In this direction, several clinic and preclinic studies point the…
(more)
▼ Adenosine and adenosine 5-trifosphate (ATP) exerts a modulatory role in inflammatory response and pain transmission. In this direction, several clinic and preclinic studies point the use of adenosine and its analogs in pain treatment, inflammatory diseases, neurological diseases and cardiopathies. The objective of this study was to analyze the modulatory action of adenosine in nociception control, as well as the possible mechanisms involved in its antinociceptive action, through the use of in vivo pharmacological studies using different nociception methods. To this end, we used male Swiss mice weighing between 25 and 35g, kept in the central byotherium of UNIVALI. The pharmacologic models used were the formalin, capsaicin, glutamate, hot plate and open field models, and the study of the mechanism of action was performed using the model of pain induced by formalin. Adenosine given intraperitonially (10-300 mg/kg), orally (50-500 mg/kg) or in the paw (50-500 μg/paw) caused dose-dependent reduction of the nociception induced by intraplantar injection of formalin, capsaincin and glutamate in mice. Moreover, adenosine (100 mg/kg, i.p.) also caused significant activity when analyzed in the hot plate model. Adenosine was effective in reducing the nociception induced by formalin when given prophilatically as well as therapeutically. The antinociceptive effect of adenosine (100 mg/kg, i.p.) was completely prevented by animal pre-treatment with caffeine (3 mg/kg, i.p.), DPCPX (5 mg/kg, i.p.), ZM241385 (3 mg/kg, i.p.), iohimbine (0,15 mg/kg, i.p.), ketanserine (1 mg/kg, i.p.), metilsergide (5 mg/kg, i.p.), L-arginine (600 mg/kg, i.p.), and haloperidol (0,2 mg/kg, i.p.), but was not affected by the pre-treatment with naloxone (1 mg/kg, i.p.), bicuculine (0,7 mg/kg, i.p.), faclofen (3 mg/kg, i.p.) or by bilateral adrenalectomy of the animals. The possible effects of adenosine on the motor performance of the animals were analyzed through the open field model. The pre-treatment of the animals with adenosine did not promote behavioural alterations when compared to control group. Taken together, these results show that adenosine presents an important antinociceptive effect and, even though its mechanism is not completely understood yet, it was observed the involvement of adenosinergic receptors A1 e A2A, L-arginine nitric oxide pathway, dopaminergic, α-2 adrenergic and serotonergic systems, but no involvement of the gabaergic or opioid systems or the AHP axis in the antinociceptive action produced by adenosine. Finally, the present study strongly indicates that adenosine has therapeutic potential in pain control and, thus, may become useful for the development of new substances with analgesic action.
A adenosina e adenosina 5-trifosfato (ATP) exercem um papel modulatório na resposta inflamatória e na transmissão dolorosa. Nesse sentido, vários estudos pré-clínicos e clínicos apontam o uso da adenosina e seus análogos no tratamento da dor, nas doenças inflamatórias, neurológicas e também em cardiopatias. O objetivo deste…
Advisors/Committee Members: Rivaldo Niero, Tania Mari Bellé Bresolin, Márcia Maria de Souza.
Subjects/Keywords: adenosina; antinocicepção; camundongos; FARMACIA; Dor - Tratamento; adenosine; antinociception; mice
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Pereira, M. A. d. S. (2005). ESTUDO DA ATIVIDADE ANTINOCICEPTIVA DA ADENOSINA EM CAMUNDONGOS - ANÁLISE DO MECANISMO DE AÇÃO. (Thesis). Universidade do Vale do Itajaí. Retrieved from http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=104
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Pereira, Márcia Alair da Silva. “ESTUDO DA ATIVIDADE ANTINOCICEPTIVA DA ADENOSINA EM CAMUNDONGOS - ANÁLISE DO MECANISMO DE AÇÃO.” 2005. Thesis, Universidade do Vale do Itajaí. Accessed February 28, 2021.
http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=104.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Pereira, Márcia Alair da Silva. “ESTUDO DA ATIVIDADE ANTINOCICEPTIVA DA ADENOSINA EM CAMUNDONGOS - ANÁLISE DO MECANISMO DE AÇÃO.” 2005. Web. 28 Feb 2021.
Vancouver:
Pereira MAdS. ESTUDO DA ATIVIDADE ANTINOCICEPTIVA DA ADENOSINA EM CAMUNDONGOS - ANÁLISE DO MECANISMO DE AÇÃO. [Internet] [Thesis]. Universidade do Vale do Itajaí; 2005. [cited 2021 Feb 28].
Available from: http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=104.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Pereira MAdS. ESTUDO DA ATIVIDADE ANTINOCICEPTIVA DA ADENOSINA EM CAMUNDONGOS - ANÁLISE DO MECANISMO DE AÇÃO. [Thesis]. Universidade do Vale do Itajaí; 2005. Available from: http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=104
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
9.
Nogueira, Thiago de Oliveira.
Efeito antinociceptivo induzido pelo glicogênio em ratos submetidos ao modelo de pressão de pata: relação com a migração neutrofílica e a expressão da proteína S100A9.
Degree: Mestrado, Patologia Experimental e Comparada, 2011, University of São Paulo
URL: http://www.teses.usp.br/teses/disponiveis/10/10133/tde-08102012-151355/
;
► A peritonite neutrofílica induzida por glicogênio acarreta antinocicepção em camundongos submetidos ao teste de contorção abdominal, a qual é mediada por uma proteína ligante de…
(more)
▼ A peritonite neutrofílica induzida por glicogênio acarreta antinocicepção em camundongos submetidos ao teste de contorção abdominal, a qual é mediada por uma proteína ligante de cálcio, com peso molecular de 14 kDa, denominada S100A9. O objetivo do presente trabalho foi aprofundar o estudo sobre o envolvimento dos neutrófilos na antinocicepção induzida pelo glicogênio em ratos submetidos ao teste de pressão de pata e avaliar a expressão da proteína S100A9 nos tempos onde foi detectado esse efeito. O glicogênio induz antinocicepção em ratos entre 2 e 12 horas após sua injeção intraplantar. O pré-tratamento dos animais com fucoidina, um inibidor de selectinas, não só reverte o efeito antinociceptivo observado como também induz hiperalgesia entre 2 e 6 horas após a injeção do glicogênio. Após 8 horas do tratamento com glicogênio, a fucoidina apenas inibiu a antinocicepção induzida pelo agente inflamatório. A análise histológica demonstrou um aumento na migração de células polimorfonucleares entre 2 e 8 horas após a administração de glicogênio, a qual foi inibida pelo pré-tratamento com fucoidina. Tanto a injeção subcutânea como intraplantar de naloxona, um inibidor inespecífico de receptores opioides, não interferiram no efeito antinociceptivo induzido pelo glicogênio, em nenhum dos tempos avaliados. Quanto à expressão da S100A9, analisada por "Western Blotting", foi observado que as amostras obtidas do coxim plantar dos animais injetados com o glicogênio, entre 2 e 12 horas, apresentaram uma banda com peso molecular aproximado de 14 kDa, o qual equivale ao peso da proteína S100A9. A quantificação das bandas marcadas com o anticorpo anti-S100A9, nos tempos entre 2 e 12 horas, demonstrou um aumento significativo da expressão dessa proteína nas amostras obtidas dos animais tratados com glicogênio, em comparação com os tratados com salina. A injeção intraperitoneal de glicogênio induziu um aumento significativo no número total de células presentes na cavidade abdominal dos animais entre a 2º e a 12º hora após o tratamento, representado pelo aumento do número de células polimorfonucleares migradas. Os sobrenadantes obtidos do exsudato peritoneal entre 2 e 12 horas após a injeção de glicogênio, administrados via intraplantar, não só reverteram a hiperalgesia induzida pela carragenina (Cg) como induziram efeito antinociceptivo. Já, o sobrenadante obtido após 24 horas da injeção de glicogênio reverteu apenas parcialmente o efeito hiperalgésico induzido pela Cg. O tratamento do sobrenadante obtido 4 horas após a injeção do glicogênio com o anticorpo anti-S100A9 aboliu totalmente o efeito antinociceptivo observado com esse sobrenadante sobre a hiperalgesia induzida pela Cg. Esses dados sugerem que a antinocicepção acarretada pelo glicogênio em ratos submetidos ao modelo de pressão de pata é dependente da migração neutrofílica, não está relacionado à liberação de peptídeos opioides, mas possivelmente à secreção da proteína S100A9 por essas células. Ainda, os resultados obtidos com os sobrenadantes do exsudato…
Advisors/Committee Members: Giorgi, Renata.
Subjects/Keywords: Antinocicepção; Antinociception; Glicogênio; Glycogen; Neutrófilos; Neutrophils; S100A9; S100A9
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Nogueira, T. d. O. (2011). Efeito antinociceptivo induzido pelo glicogênio em ratos submetidos ao modelo de pressão de pata: relação com a migração neutrofílica e a expressão da proteína S100A9. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/10/10133/tde-08102012-151355/ ;
Chicago Manual of Style (16th Edition):
Nogueira, Thiago de Oliveira. “Efeito antinociceptivo induzido pelo glicogênio em ratos submetidos ao modelo de pressão de pata: relação com a migração neutrofílica e a expressão da proteína S100A9.” 2011. Masters Thesis, University of São Paulo. Accessed February 28, 2021.
http://www.teses.usp.br/teses/disponiveis/10/10133/tde-08102012-151355/ ;.
MLA Handbook (7th Edition):
Nogueira, Thiago de Oliveira. “Efeito antinociceptivo induzido pelo glicogênio em ratos submetidos ao modelo de pressão de pata: relação com a migração neutrofílica e a expressão da proteína S100A9.” 2011. Web. 28 Feb 2021.
Vancouver:
Nogueira TdO. Efeito antinociceptivo induzido pelo glicogênio em ratos submetidos ao modelo de pressão de pata: relação com a migração neutrofílica e a expressão da proteína S100A9. [Internet] [Masters thesis]. University of São Paulo; 2011. [cited 2021 Feb 28].
Available from: http://www.teses.usp.br/teses/disponiveis/10/10133/tde-08102012-151355/ ;.
Council of Science Editors:
Nogueira TdO. Efeito antinociceptivo induzido pelo glicogênio em ratos submetidos ao modelo de pressão de pata: relação com a migração neutrofílica e a expressão da proteína S100A9. [Masters Thesis]. University of São Paulo; 2011. Available from: http://www.teses.usp.br/teses/disponiveis/10/10133/tde-08102012-151355/ ;

Penn State University
10.
Tretter, Jenelle Marie.
Effect of Atipamezole on the Antinociceptive Properties of Butorphanol and Buprenorphine Following Ketamine and Dexmedetomidine Anesthesia in C57BL/6J Mice.
Degree: 2013, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/17397
► The combination of ketamine and dexmedetomidine is often used for anesthesia of rats and mice in laboratory research. As an α2-adrenoceptor agonist, the sedative effects…
(more)
▼ The combination of ketamine and dexmedetomidine is often used for anesthesia of rats and mice in laboratory research. As an α2-adrenoceptor agonist, the sedative effects of dexmedetomidine can be reversed by administration of an α2-adrenoceptor antagonist, such as atipamezole, to speed anesthetic recovery. Opioids are often administered postoperatively for their potent analgesic effects. A previous study has shown that atipamezole may antagonize the antinociceptive effects of opioids in rats, but literature is lacking regarding the effects of atipamezole on butorphanol and buprenorphine in mice. If the antinociceptive effects of opioid analgesics are inadvertently attenuated by atipamezole, poor postoperative analgesia could have a significant impact on animal welfare, regulatory compliance and research results. A six-part study was designed to investigate the effects of atipamezole administered before butorphanol or buprenorphine, on tail-flick latency and also following ketamine-dexmedetomidine anesthesia in female C57BL/6J mice. Nociception was evaluated using the tail-flick test at 15, 30, 60, 90, 120 and 150 minutes following drug treatment. Atipamezole alone had no significant effect on tail-flick latency and no significant effect on the antinociceptive properties of butorphanol or buprenorphine in mice. Following ketamine-dexmedetomidine anesthesia, there were no significant differences in tail-flick latency values between the atipamezole and atipamezole plus butorphanol groups. Similarly, there were no significant differences in tail-flick latencies between the atipamezole and atipamezole plus buprenorphine groups following anesthesia, except at 90 and 150 minutes after treatment. These results suggest that the analgesic effects of butorphanol and buprenorphine are not affected by the reversal agent, atipamezole. However, buprenorphine should be given prior to surgery to provide adequate postoperative analgesia in C57BL/6J mice. This recommendation is supported by the late onset of buprenorphine-induced analgesia, as evidenced by increased tail-flick latencies at 90 minutes following treatment.
Advisors/Committee Members: Ronald Paul Wilson, Thesis Advisor/Co-Advisor.
Subjects/Keywords: analgesia; antinociception; tail-flick; atipamezole; butorphanol; buprenorphine; ketamine; dexmedetomidine
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Tretter, J. M. (2013). Effect of Atipamezole on the Antinociceptive Properties of Butorphanol and Buprenorphine Following Ketamine and Dexmedetomidine Anesthesia in C57BL/6J Mice. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/17397
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Tretter, Jenelle Marie. “Effect of Atipamezole on the Antinociceptive Properties of Butorphanol and Buprenorphine Following Ketamine and Dexmedetomidine Anesthesia in C57BL/6J Mice.” 2013. Thesis, Penn State University. Accessed February 28, 2021.
https://submit-etda.libraries.psu.edu/catalog/17397.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Tretter, Jenelle Marie. “Effect of Atipamezole on the Antinociceptive Properties of Butorphanol and Buprenorphine Following Ketamine and Dexmedetomidine Anesthesia in C57BL/6J Mice.” 2013. Web. 28 Feb 2021.
Vancouver:
Tretter JM. Effect of Atipamezole on the Antinociceptive Properties of Butorphanol and Buprenorphine Following Ketamine and Dexmedetomidine Anesthesia in C57BL/6J Mice. [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Feb 28].
Available from: https://submit-etda.libraries.psu.edu/catalog/17397.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Tretter JM. Effect of Atipamezole on the Antinociceptive Properties of Butorphanol and Buprenorphine Following Ketamine and Dexmedetomidine Anesthesia in C57BL/6J Mice. [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/17397
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
11.
FERRAZ, Igor Cavalcanti.
Estudo de atividades farmacológicas do óleo essencial extraído de eugenia brejoensis mazine
.
Degree: 2016, Universidade Federal de Pernambuco
URL: http://repositorio.ufpe.br/handle/123456789/18345
► A Família Myrtaceae representa uma das famílias botânicas de maior expressão nos ecossistemas brasileiros do ponto de vista farmacológico. Estudos realizados com extratos brutos de…
(more)
▼ A Família Myrtaceae representa uma das famílias botânicas de maior expressão nos
ecossistemas brasileiros do ponto de vista farmacológico. Estudos realizados com extratos
brutos de espécies pertencentes a esse gênero demonstraram a presença de propriedades
anti-inflamatórias, analgésicas, antifúngicas, hipotensora, antidiabética e antioxidante, com
base em atividades terapêuticas relatadas na literatura. O objetivo geral deste estudo foi
avaliar a atividade antinociceptiva e anti-inflamatória do óleo essencial das folhas de
Eugenia brejoensis (OEEB). Foram realizados testes de toxicidade aguda, avaliação da
atividade antinociceptiva, avaliação da performance motora e a avaliação anti-inflamatória
no tratamento oral e sistêmico. Os experimentos in vivo foram realizados com camundongos
Swiss, com idades entre 45 e 60 dias e doses de 30mg, 100mg e 300mg/kg, conforme
metodologia adotada e aprovada pelo Comitê de Ética em Pesquisa Animal da Universidade
Federal de Pernambuco. Conforme observado, o OEEB não apresentou toxicidade oral em
dose teste de 3000 mg/kg. A atividade antinociceptiva foi observada em todas as doses
testadas no modelo de contorção abdominal com diminuição significativa da quantidade de
contorções abdominais observadas. No modelo de formalina, o OEEB apresentou atividade
antinocioceptiva na fase neurogênica, nas doses de 100 e 300mg e apresentou atividade na
fase inflamatória na dose de 300mg, enquanto que no teste da capsaicina intraplantar
observou-se atividade antinociceptiva em todas as três doses estudadas. A atividade antiinflamatória,
no modelo de inflamação por óleo de cróton com tratamento sistêmico, ocorreu
apenas com a dose de 300mg, enquanto que o tratamento tópico apresentou atividade nas
doses de 100 e 300mg. Não foi observado distúrbio de marcha nos animais estudados, fato
que reforça a ação antinociceptiva nos modelos estudados.
Advisors/Committee Members: MARTINS, René Duarte (advisor), http://lattes.cnpq.br/4933620329566048 (advisor).
Subjects/Keywords: Anti-inflamatório;
Antinocicepção;
Cutia;
Myrtaceae;
Anti-inflammatory;
Antinociception;
Cutia;
Myrtaceas
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
FERRAZ, I. C. (2016). Estudo de atividades farmacológicas do óleo essencial extraído de eugenia brejoensis mazine
. (Thesis). Universidade Federal de Pernambuco. Retrieved from http://repositorio.ufpe.br/handle/123456789/18345
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
FERRAZ, Igor Cavalcanti. “Estudo de atividades farmacológicas do óleo essencial extraído de eugenia brejoensis mazine
.” 2016. Thesis, Universidade Federal de Pernambuco. Accessed February 28, 2021.
http://repositorio.ufpe.br/handle/123456789/18345.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
FERRAZ, Igor Cavalcanti. “Estudo de atividades farmacológicas do óleo essencial extraído de eugenia brejoensis mazine
.” 2016. Web. 28 Feb 2021.
Vancouver:
FERRAZ IC. Estudo de atividades farmacológicas do óleo essencial extraído de eugenia brejoensis mazine
. [Internet] [Thesis]. Universidade Federal de Pernambuco; 2016. [cited 2021 Feb 28].
Available from: http://repositorio.ufpe.br/handle/123456789/18345.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
FERRAZ IC. Estudo de atividades farmacológicas do óleo essencial extraído de eugenia brejoensis mazine
. [Thesis]. Universidade Federal de Pernambuco; 2016. Available from: http://repositorio.ufpe.br/handle/123456789/18345
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Washington State University
12.
[No author].
The Interaction Between Opioids and Cannabinoids in the Rat Periaqueductal Gray
.
Degree: 2011, Washington State University
URL: http://hdl.handle.net/2376/3475
► Opioids and cannabinoids are well known for their analgesic properties. Both classes of drugs exert their effects, in part, by activating a descending pain modulatory…
(more)
▼ Opioids and cannabinoids are well known for their analgesic properties. Both classes of drugs exert their effects, in part, by activating a descending pain modulatory pathway that includes the midbrain periaqueductal gray (PAG) and the rostral ventromedial medulla (RVM). Individually, the opioid and cannabinoid systems have been well characterized in this pathway. Cannabinoid/opioid interactions however, remain poorly understood. The aim of these studies was to characterize the interaction between opioids and cannabinoids in the descending pain pathway. Behavioral studies demonstrate that repeated morphine microinjections in the rat PAG enhance subsequent cannabinoid
antinociception, and vice versa. Furthermore, microinjections of cannabinoids into the PAG also attenuate the development of morphine tolerance. However, when cannabinoids are repeatedly injected into the RVM, they cause neurotoxic lesions. Nonetheless, acute co-administration of morphine and cannabinoids in the RVM produces greater
antinociception than when either drug is administered alone, which is consistent with earlier reports of antinociceptive synergy between the drugs. The subsequent anatomical and electrophysiological studies were conducted in order to determine the neural mechanisms underlying the bi-directional antinociceptive enhancement between cannabinoids and opioids. Confocal and electron microscopy revealed that CB1 expression in the PAG is largely somatodendritic, however CB1-labeled axons and axon terminals are widespread. CB1 and mu-opioid receptors co-localized on 32% of PAG neurons, and a subset of mu-opioid-labeled cells received appositions from (presumed presynaptic) CB1 profiles. Thus, interactions between opioids and cannabinoids are likely to occur within the same neuron, but synaptic adaptations could also occur where CB1 terminals synapse onto mu-opioid cells. Synaptic adaptations were next examined using the in vitro whole-cell patch clamp method. Previous research has shown that both cannabinoids and opioids can reduce GABAergic transmission in the PAG, and the ability of opioids to reduce GABAergic transmission is diminished in morphine tolerant animals. The present study demonstrates that chronic morphine has no effect on cannabinoid inhibition of GABAergic transmission. These results indicate a lack of cellular cross-tolerance between opioids and cannabinoids, which correlates with antinociceptive enhancement between the drugs. The results of these studies support the therapeutic potential of combined opioid/cannabinoid administration for pain relief.
Advisors/Committee Members: Morgan, Michael M (advisor).
Subjects/Keywords: Neurosciences;
analgesia;
antinociception;
cannabinoid;
opioid;
PAG;
periaqueductal gray
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
author], [. (2011). The Interaction Between Opioids and Cannabinoids in the Rat Periaqueductal Gray
. (Thesis). Washington State University. Retrieved from http://hdl.handle.net/2376/3475
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
author], [No. “The Interaction Between Opioids and Cannabinoids in the Rat Periaqueductal Gray
.” 2011. Thesis, Washington State University. Accessed February 28, 2021.
http://hdl.handle.net/2376/3475.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
author], [No. “The Interaction Between Opioids and Cannabinoids in the Rat Periaqueductal Gray
.” 2011. Web. 28 Feb 2021.
Vancouver:
author] [. The Interaction Between Opioids and Cannabinoids in the Rat Periaqueductal Gray
. [Internet] [Thesis]. Washington State University; 2011. [cited 2021 Feb 28].
Available from: http://hdl.handle.net/2376/3475.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
author] [. The Interaction Between Opioids and Cannabinoids in the Rat Periaqueductal Gray
. [Thesis]. Washington State University; 2011. Available from: http://hdl.handle.net/2376/3475
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Washington State University
13.
[No author].
The Effects of Chronic Psychostimulant Exposure on Morphine-Induced Antinociception and Tolerance
.
Degree: 2011, Washington State University
URL: http://hdl.handle.net/2376/3527
► Pre-weanling methylphenidate (MPH) exposure enhances systemic morphine-induced antinociception and tolerance in adult rats. This finding raises questions about the brain area(s) involved, the importance of…
(more)
▼ Pre-weanling methylphenidate (MPH) exposure enhances systemic morphine-induced
antinociception and tolerance in adult rats. This finding raises questions about the brain area(s) involved, the importance of developmental period during pretreatment, and whether other psychostimulants would produce similar effects. The purpose of the current studies was to address these unanswered questions. Four studies were conducted. Study 1 determined the potential involvement of the ventrolateral periaqueductal gray (vPAG) in MPH's long term enhancement of morphine-induced
antinociception and tolerance. It appears that the vPAG is not exclusively involved, since the results observed in the previously mentioned systemic study were not replicated when morphine was microinjected into the vPAG. Study 2 helped determine methamphetamine (METH) doses for subsequent studies that were high enough to produce an acute behavioral effect similar to our MPH dose, but different from saline controls. Study 3 assessed the effects of chronic periadolescent MPH and METH exposure on adult morphine-induced
antinociception and tolerance. Both age at pretreatment and psychostimulant compound used may mediate chronic MPH-induced enhancement of morphine-induced
antinociception and tolerance, since all animals showed similar acute morphine-induced
antinociception and only METH 3 mg/kg pretreated animals showed enhanced tolerance. Study 4 investigated whether morphine-induced
antinociception and tolerance were altered following chronic adult exposure to MPH and METH. Different from pre-weanling and periadolescent animals, adult exposure to METH and MPH led to an acute reduction in morphine antinociceptive potency. In summary, the results demonstrate that (1) a brain area besides the vPAG must be involved in the enhancement of morphine-induced
antinociception and tolerance observed following chronic pre-weanling MPH exposure, (2) the developmental period during which chronic psychostimulant exposure occurs impacts the degree and direction of effects on later morphine-induced
antinociception and tolerance, and (3) different psychostimulant compounds may produce differing effects on morphine tolerance when exposure occurs during the periadolescent period of ontogeny.
Advisors/Committee Members: Morgan, Michael M (advisor).
Subjects/Keywords: Psychobiology;
Pharmacology;
Neurosciences;
Antinociception;
Development;
Methamphetamine;
Methylphenidate;
Morphine;
Pain
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
author], [. (2011). The Effects of Chronic Psychostimulant Exposure on Morphine-Induced Antinociception and Tolerance
. (Thesis). Washington State University. Retrieved from http://hdl.handle.net/2376/3527
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
author], [No. “The Effects of Chronic Psychostimulant Exposure on Morphine-Induced Antinociception and Tolerance
.” 2011. Thesis, Washington State University. Accessed February 28, 2021.
http://hdl.handle.net/2376/3527.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
author], [No. “The Effects of Chronic Psychostimulant Exposure on Morphine-Induced Antinociception and Tolerance
.” 2011. Web. 28 Feb 2021.
Vancouver:
author] [. The Effects of Chronic Psychostimulant Exposure on Morphine-Induced Antinociception and Tolerance
. [Internet] [Thesis]. Washington State University; 2011. [cited 2021 Feb 28].
Available from: http://hdl.handle.net/2376/3527.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
author] [. The Effects of Chronic Psychostimulant Exposure on Morphine-Induced Antinociception and Tolerance
. [Thesis]. Washington State University; 2011. Available from: http://hdl.handle.net/2376/3527
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Washington State University
14.
[No author].
Ovarian hormone modulation of cannabinoid antinociception and cannabinoid receptor density in female rats
.
Degree: 2013, Washington State University
URL: http://hdl.handle.net/2376/4973
► Estrous cycle-related fluctuations in delta-9-tetrahydrocannabinol (THC)-induced antinociception have been observed in the rat. The aim of this study was to determine which of the major…
(more)
▼ Estrous cycle-related fluctuations in delta-9-tetrahydrocannabinol (THC)-induced antinociception have been observed in the rat. The aim of this study was to determine which of the major ovarian hormones, estradiol (E2) or progesterone (P4), modulates the antinociceptive and motoric effects of supraspinally administered THC, and whether changes in brain cannabinoid receptors (CBr) are associated with hormone modulation of THC's behavioral effects. Female rats were ovariectomized (OVX) and implanted with a cannula guide into the lateral ventricle. Vehicle (oil) or hormones (E2 or P4, or both) were administered on Days 3 and 7 after surgery. On the morning or late afternoon of Day 8 or 9, vehicle (1:1:8 ethanol:cremaphor:saline) or THC (100 μg) was administered intracerebroventricularly. Antinociception was measured using paw pressure and tail withdrawal tests at 5-180 min post-injection. Horizontal locomotion was examined in 5-min periods at 15-180 min post-injection, and catalepsy was measured at 15 and 30 min post-injection. Brain tissue was taken from separate groups of oil+oil- and E2+P4-treated females for [3H]SR141716A binding, to examine hormone effects on CBr in structures known to mediate THC's behavioral effects. THC produced antinociception on both tests, reduced locomotor activity, and produced minimal catalepsy. E2 (with or without P4) enhanced THC-induced paw pressure antinociception. Neither hormone significantly altered THC's effects on the tail withdrawal or motoric tests. CBr density in the periaqueductal gray (PAG) and caudate putamen (CPu) was increased and decreased, respectively, in E2+P4-treated females compared to oil-treated females on Day 9. Within the CPu, CBr affinity was increased in females tested on Day 8 compared to those tested on Day 9, and hormone treatment also increased affinity compared to oil treatment. Hormone treatment did not significantly alter CBr density or affinity in hypothalamus, amygdala or cerebellum.These results demonstrate that the ovarian hormone E2 (alone or with P4) enhances females' sensitivity to supraspinal THC-induced mechanical antinociception, suggesting that E2 is responsible for estrous cycle-related fluctuations in THC sensitivity. Neither ovarian hormone appears to significantly modulate the motoric effects of THC. Ovarian hormone enhancement of THC's antinociceptive effect cannot be explained by changes in CBr density or affinity in the brain areas examined.
Subjects/Keywords: Experimental psychology;
antinociception;
cannabinoid;
estradiol;
ovarian hormones;
progesterone;
rat
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
author], [. (2013). Ovarian hormone modulation of cannabinoid antinociception and cannabinoid receptor density in female rats
. (Thesis). Washington State University. Retrieved from http://hdl.handle.net/2376/4973
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
author], [No. “Ovarian hormone modulation of cannabinoid antinociception and cannabinoid receptor density in female rats
.” 2013. Thesis, Washington State University. Accessed February 28, 2021.
http://hdl.handle.net/2376/4973.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
author], [No. “Ovarian hormone modulation of cannabinoid antinociception and cannabinoid receptor density in female rats
.” 2013. Web. 28 Feb 2021.
Vancouver:
author] [. Ovarian hormone modulation of cannabinoid antinociception and cannabinoid receptor density in female rats
. [Internet] [Thesis]. Washington State University; 2013. [cited 2021 Feb 28].
Available from: http://hdl.handle.net/2376/4973.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
author] [. Ovarian hormone modulation of cannabinoid antinociception and cannabinoid receptor density in female rats
. [Thesis]. Washington State University; 2013. Available from: http://hdl.handle.net/2376/4973
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide
15.
La Vincente, Sophie.
Enhancing the use of opioids in pain management: antinociceptive potentiation with opioid agonist/antagonist combinations.
Degree: 2005, University of Adelaide
URL: http://hdl.handle.net/2440/58484
► While opioids are the most effective and widely used class of drug for the management of moderate to severe pain, their use may be limited…
(more)
▼ While opioids are the most effective and widely used class of drug for the management of moderate to severe pain, their use may be limited by adverse effects that are unpleasant and potentially dangerous. Research is increasingly directed towards strategies to improve the use of opioids in pain management, investigating methods by which the analgesia afforded by an opioid may be enhanced, while minimising adverse effects. One approach that has produced promising findings in animal studies and some clinical reports is the combination of an opioid agonist and "ultra-low" (nanomole) doses of an opioid antagonist. A recent animal study reported that
antinociception may be significantly enhanced with the combination of the partial opioid agonist/antagonist buprenorphine and ultra-low doses of the antagonist naloxone. The central aim of the studies described herein was to investigate the effect of this drug combination on response to experimental nociceptive stimuli and the incidence and severity of adverse effects among healthy volunteers.
The first study established normative responses to two commonly used nociceptive tests, the cold pressor and electrical stimulation tests, in 100 healthy volunteers. The effect of buprenorphine on nociceptive test performance had not previously been determined, therefore a dose-ranging study of buprenorphine was conducted to establish a doseresponse relationship. The subsequent two studies investigated the effect of a range of buprenorphine:naloxone IV dose ratios (5:1, 10:1, 12.5:1, 15:1, 20:1 and 25:1) on nociception and adverse effects among healthy volunteers. These studies are the first to investigate the combination of buprenorphine and ultra-low dose antagonist in humans, and the first to assess the agonist:antagonist combination in an experimental model of human nociception.
Antinociception was significantly enhanced with the combination of buprenorphine and naloxone in the 12.5:1 and 15:1 ratios. Moreover, this enhanced
antinociception occurred without a simultaneous increase in adverse effects and indeed with a reduction in the severity of some effects. An agent that produces greater analgesia and reduces adverse effects has the potential to overcome some of the barriers that limit the use of opioids in pain management. The current findings indicate that further investigation of this drug combination is warranted.
Advisors/Committee Members: Dept. of Clinical and Experimental Pharmacology (school).
Subjects/Keywords: opioids; pain management; analgesia; antinociception
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
La Vincente, S. (2005). Enhancing the use of opioids in pain management: antinociceptive potentiation with opioid agonist/antagonist combinations. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/58484
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
La Vincente, Sophie. “Enhancing the use of opioids in pain management: antinociceptive potentiation with opioid agonist/antagonist combinations.” 2005. Thesis, University of Adelaide. Accessed February 28, 2021.
http://hdl.handle.net/2440/58484.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
La Vincente, Sophie. “Enhancing the use of opioids in pain management: antinociceptive potentiation with opioid agonist/antagonist combinations.” 2005. Web. 28 Feb 2021.
Vancouver:
La Vincente S. Enhancing the use of opioids in pain management: antinociceptive potentiation with opioid agonist/antagonist combinations. [Internet] [Thesis]. University of Adelaide; 2005. [cited 2021 Feb 28].
Available from: http://hdl.handle.net/2440/58484.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
La Vincente S. Enhancing the use of opioids in pain management: antinociceptive potentiation with opioid agonist/antagonist combinations. [Thesis]. University of Adelaide; 2005. Available from: http://hdl.handle.net/2440/58484
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Kentucky
16.
Chakraborty, Ujjwal.
OPIOID CODRUGS FOR PAIN MANAGEMENT.
Degree: 2011, University of Kentucky
URL: https://uknowledge.uky.edu/chemistry_etds/2
► Pain is an unpleasant sensory and emotional experience associated with actual or potential tissus damage or described in terms of such damage. Opioids are effective…
(more)
▼ Pain is an unpleasant sensory and emotional experience associated with actual or potential tissus damage or described in terms of such damage. Opioids are effective in treating moderate to severe pain, but opioid alone therapy is associated with several adverse effects, development of tolerance and addiction potential. One way to solve these problems is to administer opioids with adjuvant drugs. In this project several opioid molecules were combined with other adjuvant drugs in a single chemical entity to form a codrug.
A series of codrugs were prepared by conjugation of an opioid with S-(-)-nornicotine, ketamine, norketamine and gabapentin. Several of the synthesized codrugs were evaluated for analgesic activity in the rats after oral administration. Codeine-S-(-)- nornicotine, 3-O-acetylmorphine-S-(-)-nornicotine, and N-ethoxycarbonylgabapentincodeine codrugs showed greater effectiveness as well as prolonged pain management properties as compared to the parent drugs. Stabilities of several synthesized codrugs were studied in aqueous solutions from pH 1.3-7.4, in simulated gastrointestinal fluids, in rat plasma and in brain homogenate. Only the ester-linked codrugs showed sign of hydrolysis in different solutions. Carbamate-linked codrugs didn’t cleave under any hydrolytic condition. Pharmacokinetic study was performed on the following three codrugs: 3-O-acetylmorphine-S-(-)-nornicotine, N-acetylgabapentin-codeine, and N-ethoxycarbonylgabapentin- codeine. The carbamate linkage in 3-O-acetylmorphine-S-(-)- nornicotine codrug did not cleave in vivo to produce parent drugs. The ester linkage in N-acetylgabapentin- codeine codrug cleaved in vivo to produce codeine and N-acetylgabapentin, but N-acetylgabapentin did not undergo hydrolysis to produce gabapentin. The ester linkage in N-ethoxycarbonylgabapentin-codeine codrug hydrolyzed slowly in plasma to produce N-ethoxycarbonylgabapentin and codeine and then the carbamate linkage in N-ethoxycarbonylgabapentin hydrolyzed even slowly to produce gabapentin. Produced codeine also metabolized to generate some amount of morphine. Thus, the design and synthesis of an opiate and gabapentin codrug was achieved which was stable enough in the gastrointestinal tract, showed enhanced analgesic effects as compared to the physical mixture of the parent drugs, and also produced the two parent drugs in blood plasma.
Subjects/Keywords: Opioid; Anticonvulsant; Codrug; Antinociception; Pharmacokinetics; Chemistry; Medicinal and Pharmaceutical Chemistry
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chakraborty, U. (2011). OPIOID CODRUGS FOR PAIN MANAGEMENT. (Doctoral Dissertation). University of Kentucky. Retrieved from https://uknowledge.uky.edu/chemistry_etds/2
Chicago Manual of Style (16th Edition):
Chakraborty, Ujjwal. “OPIOID CODRUGS FOR PAIN MANAGEMENT.” 2011. Doctoral Dissertation, University of Kentucky. Accessed February 28, 2021.
https://uknowledge.uky.edu/chemistry_etds/2.
MLA Handbook (7th Edition):
Chakraborty, Ujjwal. “OPIOID CODRUGS FOR PAIN MANAGEMENT.” 2011. Web. 28 Feb 2021.
Vancouver:
Chakraborty U. OPIOID CODRUGS FOR PAIN MANAGEMENT. [Internet] [Doctoral dissertation]. University of Kentucky; 2011. [cited 2021 Feb 28].
Available from: https://uknowledge.uky.edu/chemistry_etds/2.
Council of Science Editors:
Chakraborty U. OPIOID CODRUGS FOR PAIN MANAGEMENT. [Doctoral Dissertation]. University of Kentucky; 2011. Available from: https://uknowledge.uky.edu/chemistry_etds/2
17.
小野, 葵.
Lappaconitineの薬理学的研究 : Pharmacological study of Lappaconitine.
Degree: Chiba University / 千葉大学
URL: http://opac.ll.chiba-u.jp/da/curator/900022674/
研究科: 千葉大学大学院薬学研究科
学位:千大院薬博乙第101号
Subjects/Keywords: Lappaconitine; Antinociception; 鎮痛作用
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
小野, . (n.d.). Lappaconitineの薬理学的研究 : Pharmacological study of Lappaconitine. (Thesis). Chiba University / 千葉大学. Retrieved from http://opac.ll.chiba-u.jp/da/curator/900022674/
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
小野, 葵. “Lappaconitineの薬理学的研究 : Pharmacological study of Lappaconitine.” Thesis, Chiba University / 千葉大学. Accessed February 28, 2021.
http://opac.ll.chiba-u.jp/da/curator/900022674/.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
小野, 葵. “Lappaconitineの薬理学的研究 : Pharmacological study of Lappaconitine.” Web. 28 Feb 2021.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Vancouver:
小野 . Lappaconitineの薬理学的研究 : Pharmacological study of Lappaconitine. [Internet] [Thesis]. Chiba University / 千葉大学; [cited 2021 Feb 28].
Available from: http://opac.ll.chiba-u.jp/da/curator/900022674/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.
Council of Science Editors:
小野 . Lappaconitineの薬理学的研究 : Pharmacological study of Lappaconitine. [Thesis]. Chiba University / 千葉大学; Available from: http://opac.ll.chiba-u.jp/da/curator/900022674/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.
18.
Edfranck de Sousa Oliveira Vanderlei.
Atividades antinociceptiva e antiinflamatÃria da lectina da alga marinha verde Caulerpa cupressoides (Vahl) C. Agardh var. lycopodium em animais.
Degree: Master, 2008, Universidade Federal do Ceará
URL: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=3537
;
► A busca de novos compostos alternativos no controle da dor e da inflamaÃÃo, com mÃnimos efeitos colaterais, tem despertado o interesse pelas algas marinhas. O…
(more)
▼ A busca de novos compostos alternativos no controle da dor e da inflamaÃÃo, com mÃnimos efeitos colaterais, tem despertado o interesse pelas algas marinhas. O objetivo desse trabalho foi investigar o potencial antinociceptivo e antiinflamatÃrio da lectina da alga marinha verde Caulerpa cupressoides (Vahl) C. Agardh var. lycopodium (LCc) em animais. A LCc, apresentando atividade hemaglutinante contra eritrÃcitos tripsinizados de coelho, foi obtida a partir da aplicaÃÃo do extrato protÃico total em procedimentos cromatogrÃficos de troca-iÃnica em coluna de DEAE-celulose e de afinidade em coluna de Sephadex G-100. A seguir, foi utilizada nos ensaios de nocicepÃÃo e inflamaÃÃo, usando camundongos Swiss e ratos Wistar, respectivamente. A LCc foi administrada 30 min antes de cada estÃmulo nocigÃnico, ou seja, antes da injeÃÃo i.p. de Ãcido acÃtico a 0,8% (10 Âl/ml), da injeÃÃo intraplantar da formalina a 1% (20 Âl/pata) ou do teste da Placa Quente (51Â1 ÂC), e seu efeito comparado a dos animais nÃo tratados (Salina) ou prÃ-tratados s.c. com Indometacina ou Morfina, ambas a 5 mg/kg. Observou-se que a LCc (3, 9 e 27 mg/kg; i.v.) reduziu significantemente o nÃmero de contorÃÃes abdominais induzidas por Ãcido acÃtico em 37,2%; 53,5% e 86,0%, respectivamente. LCc (27 mg/kg) tambÃm reduziu (p<0,05) a fase 1 (neurogÃnica) e a fase 2 (inflamatÃria) induzidas pela formalina, em 45,3% e 86,3%, respectivamente. A LCc (27 mg/kg), entretanto, nÃo foi capaz de reduzir a nocicepÃÃo avaliada no teste da Placa Quente, quando comparada à morfina. Para confirmar a atividade da LCc, verificou-se que os efeitos antinociceptivos foram abolidos quando a LCc foi prÃ-incubada com a glicoproteÃna mucina (2 mg/ml), inibidora de sua atividade hemaglutinante. Sugere-se, portanto, que a atividade antinociceptiva observada foi, de fato, devido à LCc e que essa atividade ocorra predominante via inibiÃÃo de mecanismos perifÃricos. Em seguida, realizou-se o ensaio da migraÃÃo de leucÃcitos na cavidade peritoneal induzida por Carragenina (Cg-tipo λ ; 700 Âg/cavidade), onde se observou que a administraÃÃo da LCc (9 mg/kg; i.v.) 30 min antes da Cg, reduziu significativamente a contagem do nÃmero de neutrÃfilos em 65,9%. Finalmente, a LCc (9 mg/kg), foi administrada em camundongos machos Swiss diariamente por 7 dias e no 8 dia amostras sanguÃneas foram coletadas para dosagens sÃricas de urÃia e transaminases (TGO e TGP), e remoÃÃo de ÃrgÃos para avaliaÃÃo da relaÃÃo peso ÃrgÃo/peso corporal. Observou-se que a LCc nÃo causou alteraÃÃes hepÃticas ou renais, visto que nÃo determinou alteraÃÃes, de forma significante, nas atividades das transaminases TGO (Salina=29,44Â3,193; LCc=36,00Â21,98 U/l) e TGP (Salina=13,59Â3,373; LCc=17,64Â2,676 U/l), nem dos nÃveis de urÃia (Salina=224,3Â10,84; LCc=270,0Â24,00 U/l), alÃm de nÃo determinar variaÃÃo significante do peso Ãmido dos respectivos ÃrgÃos: fÃgado (Salina=5,23Â0,195; LCc=6,02Â0,100), rim (Salina=0,840Â0,015; LCc=0,851Â0,065) e coraÃÃo (Salina=0,568Â0,055; LCc=0,639 0,039). Em resumo, conclui-se que a LCc…
Advisors/Committee Members: Vilma de Lima, Marjory Lima Holanda, Norma Maria Barros Benevides.
Subjects/Keywords: BIOQUIMICA; Alga marinha; Lectina; Caulerpa cupressoides; AntinocicepÃÃo; MigraÃÃo; Marine alga; Lectin; Caulerpa cupressoides; Antinociception; Migration
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APA ·
Chicago ·
MLA ·
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APA (6th Edition):
Vanderlei, E. d. S. O. (2008). Atividades antinociceptiva e antiinflamatÃria da lectina da alga marinha verde Caulerpa cupressoides (Vahl) C. Agardh var. lycopodium em animais. (Masters Thesis). Universidade Federal do Ceará. Retrieved from http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=3537 ;
Chicago Manual of Style (16th Edition):
Vanderlei, Edfranck de Sousa Oliveira. “Atividades antinociceptiva e antiinflamatÃria da lectina da alga marinha verde Caulerpa cupressoides (Vahl) C. Agardh var. lycopodium em animais.” 2008. Masters Thesis, Universidade Federal do Ceará. Accessed February 28, 2021.
http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=3537 ;.
MLA Handbook (7th Edition):
Vanderlei, Edfranck de Sousa Oliveira. “Atividades antinociceptiva e antiinflamatÃria da lectina da alga marinha verde Caulerpa cupressoides (Vahl) C. Agardh var. lycopodium em animais.” 2008. Web. 28 Feb 2021.
Vancouver:
Vanderlei EdSO. Atividades antinociceptiva e antiinflamatÃria da lectina da alga marinha verde Caulerpa cupressoides (Vahl) C. Agardh var. lycopodium em animais. [Internet] [Masters thesis]. Universidade Federal do Ceará 2008. [cited 2021 Feb 28].
Available from: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=3537 ;.
Council of Science Editors:
Vanderlei EdSO. Atividades antinociceptiva e antiinflamatÃria da lectina da alga marinha verde Caulerpa cupressoides (Vahl) C. Agardh var. lycopodium em animais. [Masters Thesis]. Universidade Federal do Ceará 2008. Available from: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=3537 ;
19.
Flávia Negromonte Souto Maior.
Atividade ansiolítica e antinociceptiva do óxido de linalol em modelos animais.
Degree: 2011, Universidade Federal da Paraíba
URL: http://bdtd.biblioteca.ufpb.br/tde_busca/arquivo.php?codArquivo=1867
► O óxido de linalol (OXL) é um monoterpeno, álcool monocíclico, de odor agradável, que pode ser encontrado em óleos essenciais de algumas plantas aromáticas. Pode…
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▼ O óxido de linalol (OXL) é um monoterpeno, álcool monocíclico, de odor agradável, que pode ser encontrado em óleos essenciais de algumas plantas aromáticas. Pode também ser obtido, a partir do linalol, por oxidação natural ou processos sintéticos. A ausência de pesquisas sobre as possíveis atividades farmacológicas do OXL incentivou à realização deste traballho, que teve como objetivo avaliar a atividade ansiolítica e antinociceptiva do OXL em camundongos Swiss machos. Inicialmente, foi realizada a pesquisa da dose letal 50 (DL50) do OXL, no intuito de estabelecer doses e concentrações relativamente seguras para os testes subsequentes. O OXL foi utilizado nos experimentos nas doses de 50, 100 e 150 mg/kg, pela via intraperitoneal (i.p.) e nas concentrações de 0,65%, 1,25%, 2,5% e 5,0%, pela via inalatória (v.i.). Para investigar o perfil de ação deste monoterpeno no sistema nervoso central foram realizados testes gerais como triagem farmacológica comportamental e teste da barra giratória. Durante a triagem, a analgesia foi o principal efeito observado nos animais tratados com OXL i.p. e v.i. Houve também aumento nos comportamentos de levantar e escalar nos animais que inalaram OXL. No teste da barra giratória foi observado que o OXL i.p. e v.i. não causou prejuízos à coordenação motora dos animais. Durante a realização de testes específicos, o OXL v.i., apresentou um perfil de droga ansiolítica, aumentando o tempo de permanência dos animais nos braços abertos do labirinto em cruz elevado e no compartimento iluminado do aparelho de claro-escuro. A droga padrão utilizada nesses modelos animais de ansiedade foi o diazepam. O OXL i.p. apresentou um perfil de droga antinociceptiva, diminuindo o número de contorções abdominais induzidas pelo ácido acético e o tempo de lambida da pata dos animais, nas duas fases de observação do teste da formalina. Nestes testes, a morfina foi usada como droga padrão. Para tentar elucidar o mecanismo envolvido no efeito antinociceptivo do OXL foram usadas ferramentas farmacológicas como naloxona, atropina, sulpirida e cafeína. O efeito antinociceptivo do OXL foi revertido pela naloxona e sulpirida na primeira fase do teste da formalina, e pela cafeína, em ambas as fases, sugerido o envolvimento de transmissão opióde, dopaminérgica e adenosínica na ação antinociceptiva. O desenvolvimento deste trabalho apresentou descobertas preliminares de atividades psicofarmacológicas do OXL. Outras investigações com este monoterpeno podem levar, no futuro, ao desenvolvimento de um novo medicamento ou nova molécula com maior potência e seletividade.
Linalool oxide (OXL) is a monoterpene, monocyclic alcohol, which has pleasant odor and can be found in essential oils of some aromatic plants. It can also be obtained from linalool by natural oxidation or synthetic processes. The lack of research on possible pharmacological activities of OXL encouraged this work that had as main objective the assessment of anxiolytic-like and antinociceptive-like activities of OXL on male Swiss mice. Initially was…
Advisors/Committee Members: Reinaldo Nobrega de Almeida.
Subjects/Keywords: Antinociceptio; Ansiolítico; Psicofarmacologia; Óxido de linalol; Farmacologia; FARMACOLOGIA; Pharmacology; Linalool oxide; Psychopharmacology; Anxiolytic; Antinociception
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Maior, F. N. S. (2011). Atividade ansiolítica e antinociceptiva do óxido de linalol em modelos animais. (Thesis). Universidade Federal da Paraíba. Retrieved from http://bdtd.biblioteca.ufpb.br/tde_busca/arquivo.php?codArquivo=1867
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Maior, Flávia Negromonte Souto. “Atividade ansiolítica e antinociceptiva do óxido de linalol em modelos animais.” 2011. Thesis, Universidade Federal da Paraíba. Accessed February 28, 2021.
http://bdtd.biblioteca.ufpb.br/tde_busca/arquivo.php?codArquivo=1867.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Maior, Flávia Negromonte Souto. “Atividade ansiolítica e antinociceptiva do óxido de linalol em modelos animais.” 2011. Web. 28 Feb 2021.
Vancouver:
Maior FNS. Atividade ansiolítica e antinociceptiva do óxido de linalol em modelos animais. [Internet] [Thesis]. Universidade Federal da Paraíba; 2011. [cited 2021 Feb 28].
Available from: http://bdtd.biblioteca.ufpb.br/tde_busca/arquivo.php?codArquivo=1867.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Maior FNS. Atividade ansiolítica e antinociceptiva do óxido de linalol em modelos animais. [Thesis]. Universidade Federal da Paraíba; 2011. Available from: http://bdtd.biblioteca.ufpb.br/tde_busca/arquivo.php?codArquivo=1867
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
20.
Marlova Manhabosco Dal Molin.
Isolamento, identificação e avaliação farmacológica de extratos, frações e compostos obtidos das partes aéreas da Garcinia achachairu Rusby (Clusiaceae).
Degree: 2009, Universidade do Vale do Itajaí
URL: http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=745
► Garcinia achachairu Rusby é uma planta pertencente ao gênero Garcinia (ex-Rheedia), conhecida popularmente como achachairu e utilizada na medicina popular no tratamento de reumatismo, inflamação…
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▼ Garcinia achachairu Rusby é uma planta pertencente ao gênero Garcinia (ex-Rheedia), conhecida popularmente como achachairu e utilizada na medicina popular no tratamento de reumatismo, inflamação e distúrbios gástricos. Algumas das espécies deste gênero apresentam diferentes classes químicas tais como benzofenonas e biflavonóides de grande importância para a indústria farmacêutica. No entanto, poucos estudos científicos são encontrados na literatura tanto da parte química quanto biológica. O presente estudo teve como objetivo isolar e identificar os principais constituintes químicos presentes nas partes aéreas bem como avaliar o potencial biológico de alguns extratos, frações e substâncias puras. Neste sentido, as partes aéreas (sementes, folhas e galhos) foram, secas a foram secas a 40 °C e separadamente maceradas em metanol a temperatura ambiente, para obtenção dos respectivos extratos metanólicos brutos (EMB). O EMB das folhas sucessivamente particionado com solventes de polaridade crescente como: hexano, clorofórmio e acetato de etila. Subsequentemente, o EMB sementes e as frações obtidas das folhas, foram submetidos à purificação através de cromatografia em coluna (CC) e monitorados por cromatografia em camada delgada (CCD). Os compostos isolados foram identificados por métodos espectroscópicos convencionais de identificação (IV, RMN-H1 e C13). Os seguintes compostos foram identificados: uma benzofenona prenilada denominada de gutiferona A e dois biflavonóides denominados de GB1a e a Amentoflavona. Os extratos foram avaliados quanto ao seu efeito antiulcerogênico através do experimento da atividade antiulcera induzida por etanol em camundongos. Os extratos, frações e Gutiferona A foram avaliados quanto ao seu efeito antinociceptivo em diferentes modelos experimentais em camundongos. A maioria das amostras avaliadas demostraram perfil analgésico no modelo da acido acético, formalina, capsaicina e glutamato. No entanto, o EMB das sementes apresentou uma DI50 de 13,1mg/Kg e inibição Máxima de 724% no modelo de nocicepção induzida pelo acido acético. Neste mesmo modelo, Gutiferona A apresentou uma DI50 de 4,54 (3,29 -6,24) mg/Kg e IM de 735%, sendo cerca de cinco vezes mais potente do que a aspirina e o paracetamol, dois medicamentos usados em comparação. Quando avaliado a atividade antiulcerogênica induzida por etanol, todos os extratos metanólicos reduziram estatisticamente a área total ulcerada (ATU) e o índice de lesões ulcerativas (ILU). No entanto, o extrato obtido das sementes foi mais efetivo com inibições de 74,1 e 54,7 % para ATU e ILU, respectivamente. Estas inibições foram similares ao omeprazol, um medicamento usado como controle. Estes em conjunto confirmam o uso de G. achachairu na medicina popular e como uma fonte importante de moléculas bioativas
Rheedia achachairu Rusby is a plant belonging to the genus Garcinia (ex Rheedia), popularly known as "achachairu" and used in folk medicine to treat rheumatism, inflammation, and gastric disorders. Some of the species of this genus have different chemical…
Advisors/Committee Members: Nara Lins Meira Quintão, Sérgio Faloni de Andrade, Rosendo Augusto Yunes, Rivaldo Niero.
Subjects/Keywords: garcinia achachairu; antinocicepção; antiúlcera; gutiferona A; FARMACIA; garcinia achachairu; antinociception; antiulcer; gutifferone A
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Molin, M. M. D. (2009). Isolamento, identificação e avaliação farmacológica de extratos, frações e compostos obtidos das partes aéreas da Garcinia achachairu Rusby (Clusiaceae). (Thesis). Universidade do Vale do Itajaí. Retrieved from http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=745
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Molin, Marlova Manhabosco Dal. “Isolamento, identificação e avaliação farmacológica de extratos, frações e compostos obtidos das partes aéreas da Garcinia achachairu Rusby (Clusiaceae).” 2009. Thesis, Universidade do Vale do Itajaí. Accessed February 28, 2021.
http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=745.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Molin, Marlova Manhabosco Dal. “Isolamento, identificação e avaliação farmacológica de extratos, frações e compostos obtidos das partes aéreas da Garcinia achachairu Rusby (Clusiaceae).” 2009. Web. 28 Feb 2021.
Vancouver:
Molin MMD. Isolamento, identificação e avaliação farmacológica de extratos, frações e compostos obtidos das partes aéreas da Garcinia achachairu Rusby (Clusiaceae). [Internet] [Thesis]. Universidade do Vale do Itajaí; 2009. [cited 2021 Feb 28].
Available from: http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=745.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Molin MMD. Isolamento, identificação e avaliação farmacológica de extratos, frações e compostos obtidos das partes aéreas da Garcinia achachairu Rusby (Clusiaceae). [Thesis]. Universidade do Vale do Itajaí; 2009. Available from: http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=745
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
21.
Santos, Yara Fabrini dos.
Papel do complexo receptor glutamato/NMDA e óxido nítrico no corno dorsal da medula espinal da antinocicepção induzida pelo medo.
Degree: Mestrado, Psicobiologia, 2010, University of São Paulo
URL: http://www.teses.usp.br/teses/disponiveis/59/59134/tde-13102010-211056/
;
► Quando confrontado com situações de medo os roedores apresentam respostas comportamentais (ex., luta, fuga, imobilidade e vocalização) e neurovegetativas (taquicardia, hipertensão e defecação) que caracterizam…
(more)
▼ Quando confrontado com situações de medo os roedores apresentam respostas comportamentais (ex., luta, fuga, imobilidade e vocalização) e neurovegetativas (taquicardia, hipertensão e defecação) que caracterizam a reação de defesa. Em geral essas respostas são acompanhadas de antinocicepção. Estudos demonstram um papel do óxido nítrico (NO) e de receptores NMDA (N-metil-D-aspartato) na mediação de respostas nociceptivas no corno dorsal da medula espinal. Resultados do nosso laboratório demonstraram que a exposição a uma situação ameaçadora, como o labirinto em cruz elevado aberto ou sem paredes (LCEa), provoca antinocicepção de alta magnitude em ratos e camundongos. Assim, o presente estudo teve por objetivo investigar o papel do complexo receptor glutamato/NMDA e NO no corno dorsal da medula espinal na resposta antinociceptiva induzida pela exposição ao LCEa. Camundongos receberam injeção por via intratecal (i.t.) de NMDA (0; 0,4 ou 0,8 nmol/5,0 l) para avaliar seus efeitos intrínsecos sobre a nocicepção. Enquanto a dose de 0,8 nmol de NMDA provocou efeitos nociceptivos, a dose de 0,4 nmol se mostrou desprovida de efeitos. Em seguida, nosso estudo avaliou os efeitos do NMDA (0; 0,1; 0,2 ou 0,4 nmol, i.t.) na nocicepção induzida pela injeção de formalina 2,5% na pata traseira direita do camundongo. Nenhuma dose de NMDA aumentou o tempo de lambidas na pata durante os 10 minutos do teste. Assim, investigamos os efeitos da injeção i.t. de NMDA (0; 0,1; 0,2 ou 0,4 nmol) na antinocicepção induzida pela exposição ao ambiente aversivo (LCEa) ou não aversivo (LCE fechado: quatro braços com paredes; LCEf) em camundongos pré-tratados com formalina a 2,5% na pata traseira direita, durante 10 minutos. O tratamento com NMDA (0,4 nmol) reverteu parcialmente a antinocicepção induzida pela exposição ao LCEa, sem afetar a resposta dos animais expostos ao LCEf. Para avaliar se os efeitos anti-antinociceptivos do NMDA (0,4 nmol) dependem da síntese de NO, camundongos receberam injeção i.t. combinada de L-NAME (N-nitro-L-arginina-metil-éster), um inibidor da NOS, e NMDA. O pré-tratamento com L-NAME (40 nmoles/5,0 l i.t.) bloqueou seletivamente os efeitos anti-antinociceptivos do NMDA. Tomados em conjunto, nossos resultados sugerem que a antinocicepção induzida pela exposição ao LCEa pode ser parcialmente revertida pela ativação de receptores NMDA e indicam que esse efeito depende da síntese de NO no corno dorsal da medula espinal de camundongos.
Rodents exposed to threatening situations (e.g., prey-predator interactions) usually display defensive behaviors (e.g., fight, flight, freezing, vocalization), and neurovegetative (e.g., tachycardia, hypertension, defecation) responses characterized as a fear reaction. Commonly, these responses are accompanied by antinociception. Evidence showing that the glutamate NMDA (N-methyl-d-aspartate) receptor and nitric oxide (NO) complex located within the dorsal horn of the spinal cord in the mediation of the nociceptive response have instigated researchers to investigate the role of the NMDA/NO on…
Advisors/Committee Members: Souza, Ricardo Luiz Nunes de.
Subjects/Keywords: antinocicepçao; antinociception; corno dorsal; dorsal horn; Glutamate; Glutamato; medo; mice; NMDA; NMDA; NO
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Santos, Y. F. d. (2010). Papel do complexo receptor glutamato/NMDA e óxido nítrico no corno dorsal da medula espinal da antinocicepção induzida pelo medo. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/59/59134/tde-13102010-211056/ ;
Chicago Manual of Style (16th Edition):
Santos, Yara Fabrini dos. “Papel do complexo receptor glutamato/NMDA e óxido nítrico no corno dorsal da medula espinal da antinocicepção induzida pelo medo.” 2010. Masters Thesis, University of São Paulo. Accessed February 28, 2021.
http://www.teses.usp.br/teses/disponiveis/59/59134/tde-13102010-211056/ ;.
MLA Handbook (7th Edition):
Santos, Yara Fabrini dos. “Papel do complexo receptor glutamato/NMDA e óxido nítrico no corno dorsal da medula espinal da antinocicepção induzida pelo medo.” 2010. Web. 28 Feb 2021.
Vancouver:
Santos YFd. Papel do complexo receptor glutamato/NMDA e óxido nítrico no corno dorsal da medula espinal da antinocicepção induzida pelo medo. [Internet] [Masters thesis]. University of São Paulo; 2010. [cited 2021 Feb 28].
Available from: http://www.teses.usp.br/teses/disponiveis/59/59134/tde-13102010-211056/ ;.
Council of Science Editors:
Santos YFd. Papel do complexo receptor glutamato/NMDA e óxido nítrico no corno dorsal da medula espinal da antinocicepção induzida pelo medo. [Masters Thesis]. University of São Paulo; 2010. Available from: http://www.teses.usp.br/teses/disponiveis/59/59134/tde-13102010-211056/ ;

Universidade Federal de Santa Maria
22.
Gabriela Trevisan dos Santos.
CARACTERIZAÇÃO DO ESTERÓIDE α-ESPINASTEROL COMO UM NOVO ANTAGONISTA DO RECEPTOR TRPV1 COM EFEITO ANTINOCICEPTIVO.
Degree: 2011, Universidade Federal de Santa Maria
URL: http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=3985
► O receptor de potencial transitório vanilóide 1 (TRPV1) é relevante para a percepção de estímulos nocivos e tem sido estudado como um alvo terapêutico para…
(more)
▼ O receptor de potencial transitório vanilóide 1 (TRPV1) é relevante para a percepção de estímulos nocivos e tem sido estudado como um alvo terapêutico para o desenvolvimento de novos analgésicos. O objetivo deste estudo foi desenvolver uma triagem in vivo e in vitro para caracterizar novos antagonistas do receptor TRPV1 isolados das folhas de Vernonia Tweedieana Baker, uma planta medicinal, com atividade antinociceptiva em camundongos. Todas as frações e o extrato hidroalcólico apresentaram efeito antinociceptivo no teste da capsaicina, sendo que a fração diclorometano (Dcm) também mostrou efeito antiedematogênico. Entre os compostos isolados da fração Dcm, apenas o α-espinasterol reduziu a nocicepção e o edema induzidos pela injeção intraplantar de capsaicina. Além disso, o α- espinasterol foi capaz de deslocar o radioligante [3H]-resiniferatoxina, e também de diminuir o influxo de cálcio estimulado pela capsaicina. A fração Dcm e o composto α-espinasterol apresentaram efeito anti-hiperalgésico na nocicepção induzida por estímulo térmico, mas não induzida por estímulo mecânico em animais sem injúria. Porém, o composto α-espinasterol não apresentou atividade antinociceptiva em animais pré-tratados sistemicamente com resiniferatoxina. Este composto e a fração Dcm foram capazes de reduzir a hiperalgesia mecânica e térmica, e também o edema induzidos por adjuvante completo de Freund. A fração Dcm e o α- espinasterol não foram capazes de induzir alteração na temperatura corporal ou atividade locomotora. Também, o α-espinasterol mostrou boa absorção por via oral, e alta penetração no cérebro e na medula espinhal de camundongos. Assim, o α- espinasterol, isolado da fração Dcm, age como um antagonista do receptor TRPV1 com eficaz efeito antinociceptivo, sem indução de efeitos adversos.
The transient receptor potential vanilloid 1 (TRPV1) is relevant to the perception of noxious information and has been studied as a therapeutic target for the development of new analgesics. The goal of this study was to perform in vivo and in vitro screens to identify novel, efficacious, and safe TRPV1 antagonists isolated from leaves of the medicinal plant Vernonia tweedieana Baker. All of the fractions and the hydroalcoholic extract produced antinociception in mice during the capsaicin test, but the dichloromethane fraction (Dcm) also had antioedematogenic effect. Among the compounds isolated from the Dcm fraction, only α-spinasterol reduced the nociception and oedema induced by capsaicin injection. Moreover, α-spinasterol demonstrated good oral absorption and high penetration into the brain and spinal cord of mice. Besides, α-spinasterol was able to displace [3H]-resiniferatoxin (RTX) binding and diminish calcium (Ca2+) influx mediated by capsaicin. Orally administration of the Dcm fraction and α-spinasterol also produced antinociceptive effect in the noxious heat-induced nociception test; however, they did not change the mechanical threshold of naive mice. The treatment with…
Advisors/Committee Members: Roselei Fachinetto, Maria Rosa Chitolina Schetinger, Juliano Ferreira.
Subjects/Keywords: capsaicina; TRPV1; Esteróide; vanilóide; antinocicepção; Vernonia; CIENCIAS BIOLOGICAS; Steroid; TRPV1; capsaicin; vanilloid; antinociception; Vernonia
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Santos, G. T. d. (2011). CARACTERIZAÇÃO DO ESTERÓIDE α-ESPINASTEROL COMO UM NOVO ANTAGONISTA DO RECEPTOR TRPV1 COM EFEITO ANTINOCICEPTIVO. (Thesis). Universidade Federal de Santa Maria. Retrieved from http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=3985
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Santos, Gabriela Trevisan dos. “CARACTERIZAÇÃO DO ESTERÓIDE α-ESPINASTEROL COMO UM NOVO ANTAGONISTA DO RECEPTOR TRPV1 COM EFEITO ANTINOCICEPTIVO.” 2011. Thesis, Universidade Federal de Santa Maria. Accessed February 28, 2021.
http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=3985.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Santos, Gabriela Trevisan dos. “CARACTERIZAÇÃO DO ESTERÓIDE α-ESPINASTEROL COMO UM NOVO ANTAGONISTA DO RECEPTOR TRPV1 COM EFEITO ANTINOCICEPTIVO.” 2011. Web. 28 Feb 2021.
Vancouver:
Santos GTd. CARACTERIZAÇÃO DO ESTERÓIDE α-ESPINASTEROL COMO UM NOVO ANTAGONISTA DO RECEPTOR TRPV1 COM EFEITO ANTINOCICEPTIVO. [Internet] [Thesis]. Universidade Federal de Santa Maria; 2011. [cited 2021 Feb 28].
Available from: http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=3985.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Santos GTd. CARACTERIZAÇÃO DO ESTERÓIDE α-ESPINASTEROL COMO UM NOVO ANTAGONISTA DO RECEPTOR TRPV1 COM EFEITO ANTINOCICEPTIVO. [Thesis]. Universidade Federal de Santa Maria; 2011. Available from: http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=3985
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade Federal de Santa Maria
23.
Julie Maria Milano.
AVALIAÇÃO DO POTENCIAL ANTINOCICEPTIVO DE 5- TRIALOMETIL- 4,5-DIIDRO-1H- PIRAZOL METIL ÉSTERES INÉDITOS EM CAMUNDONGOS.
Degree: 2008, Universidade Federal de Santa Maria
URL: http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=2159
► A dor é um sintoma comum na prática clínica, por isso muitos avanços estão sendo realizados no sentido de obter moléculas analgésicas cada vez mais…
(more)
▼ A dor é um sintoma comum na prática clínica, por isso muitos avanços estão sendo realizados no sentido de obter moléculas analgésicas cada vez mais efetivas e com menos efeitos colaterais. Neste contexto, no presente estudo avaliou-se o potencial antinociceptivo de quatro pirazóis inéditos: 3- metil-5-hidroxi-5-trifluormetil-4,5-diidro- 1H-pirazol metil éster (MPF3), 4-metil-5-hidroxi-5-trifluormetil-4,5-diidro-1H-pirazol metil éster (MPF4), 3-metil-5-hidroxi-5-triclorometil-4,5-diidro-1H-pirazol metil éster (MPCl3) e 4-metil-5-hidroxi-5-triclorometil-4,5-diidro-1H-pirazol metil éster (MPCl4). A administração sistêmica dos compostos foi efetiva em inibir a nocicepção em modelos de dor induzida por estímulo nocivo químico (teste da formalina, 0,03-1,0 mmol/kg, i.p.) e térmico (teste da placa-quente, 0,1-1,0 mmol/kg, i.p.). Em adição, MPF4 produziu antinocicepção em modelos de dor inflamatória causada por Adjuvante Completo de Freund (ACF) ou por incisão na pata de camundongos. O efeito antinociceptivo de MPF4 (1,0 mmol/kg, i.p.) não foi revertido pelo prétratamento dos animais com ioimbina (0,15 mg/kg, i.p.) ou p-clorofenilalanina etil éster (PCPA; 300 mg/kg, i.p.), mas sim, por naloxona (2,0 mg/kg, i.p.), tanto na nocicepção térmica quanto na nocicepção química. O tratamento dos animais durante um período de 8 dias consecutivos com MPF4 (1,0 mmol/kg, i.p), ao contrário daqueles tratados com morfina (5,0 mg/kg, i.p.), não desenvolveram tolerância antinociceptiva nem tolerância cruzada com os animais tolerantes à morfina. Porém, similar ao opióide morfina (11 mg/kg, i.p.), MPF4 (1,0 mmol/kg, i.p) inibiu o trânsito gastrintestinal de camundongos, sendo este efeito revertido por naloxona (2,5 mg/kg, i.p.). Além disso, diferente de indometacina (0,1 mmol/kg, v.o.), MPF4 (1,0 mmol/kg, v.o.) não induziu lesão gástrica em camundongos. Nenhum dos compostos testados causou alteração na atividade locomotora dos camundongos. Estes achados sugerem que os novos pirazoline metil ésteres avaliados parecem ser promissores para o desenvolvimento de novas drogas analgésicas terapeuticamente relevantes.
Pain is a common symptom in clinical practice and many advances have been observed in order to obtain more effective analgesic molecules with fewer side effects. The present study evaluated the antinociceptive potential of four novel pyrazoles: 3-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPF3), 4-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPF4), 3-methyl-5-trichloromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPCl3), and 4-methyl-5-trichloromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPCl4). The systemic administration of the compounds was effective for the inhibition of the nociception in chemical (formalin test, 0.03 -1.0 mmol/kg, i.p.) and thermal (hot-plate test, 0.1-1.0 mmol/kg, i.p.) models of pain. In addition, MPF4 also produced antinociception in models of inflammatory pain induced by Complete Freunds Adjuvant (CFA) or by incision procedure in…
Advisors/Committee Members: Tatiana Emanuelli, Maria Rosa Chitolina Schetinger, Helio Gauze Bonacorso, Nilo Zanatta, Maribel Antonello Rubin, Carla Dalmaz.
Subjects/Keywords: antinocicepção; analgésicos; dor; pirazoline metil ésters; BIOQUIMICA; antinociception; pyrazoline methyl esteres; pain; analgesics
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Milano, J. M. (2008). AVALIAÇÃO DO POTENCIAL ANTINOCICEPTIVO DE 5- TRIALOMETIL- 4,5-DIIDRO-1H- PIRAZOL METIL ÉSTERES INÉDITOS EM CAMUNDONGOS. (Thesis). Universidade Federal de Santa Maria. Retrieved from http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=2159
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Milano, Julie Maria. “AVALIAÇÃO DO POTENCIAL ANTINOCICEPTIVO DE 5- TRIALOMETIL- 4,5-DIIDRO-1H- PIRAZOL METIL ÉSTERES INÉDITOS EM CAMUNDONGOS.” 2008. Thesis, Universidade Federal de Santa Maria. Accessed February 28, 2021.
http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=2159.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Milano, Julie Maria. “AVALIAÇÃO DO POTENCIAL ANTINOCICEPTIVO DE 5- TRIALOMETIL- 4,5-DIIDRO-1H- PIRAZOL METIL ÉSTERES INÉDITOS EM CAMUNDONGOS.” 2008. Web. 28 Feb 2021.
Vancouver:
Milano JM. AVALIAÇÃO DO POTENCIAL ANTINOCICEPTIVO DE 5- TRIALOMETIL- 4,5-DIIDRO-1H- PIRAZOL METIL ÉSTERES INÉDITOS EM CAMUNDONGOS. [Internet] [Thesis]. Universidade Federal de Santa Maria; 2008. [cited 2021 Feb 28].
Available from: http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=2159.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Milano JM. AVALIAÇÃO DO POTENCIAL ANTINOCICEPTIVO DE 5- TRIALOMETIL- 4,5-DIIDRO-1H- PIRAZOL METIL ÉSTERES INÉDITOS EM CAMUNDONGOS. [Thesis]. Universidade Federal de Santa Maria; 2008. Available from: http://coralx.ufsm.br/tede/tde_busca/arquivo.php?codArquivo=2159
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Virginia Commonwealth University
24.
Kwilasz, Andrew.
Effect of cannabinoids on pain-stimulated and pain-depressed behavior in rats.
Degree: PhD, Pharmacology & Toxicology, 2013, Virginia Commonwealth University
URL: https://doi.org/10.25772/SRD1-6Q02
;
https://scholarscompass.vcu.edu/etd/486
► Cannabinoids produce antinociception in many preclinical models of acute and chronic pain. In contrast, cannabinoids produce inconsistent analgesia in humans, showing little or no efficacy…
(more)
▼ Cannabinoids produce
antinociception in many preclinical models of acute and chronic pain. In contrast, cannabinoids produce inconsistent analgesia in humans, showing little or no efficacy in treating acute pain, with modest efficacy in treating chronic inflammatory pain. This discrepancy may reflect an overreliance on preclinical assays of pain-stimulated behaviors, defined as behaviors that increase in rate or intensity following delivery of a noxious stimulus. In these assays,
antinociception is indicated by a reduction in pain-stimulated behaviors, and
antinociception is produced either by a reduction in sensory sensitivity to the noxious stimulus (i.e. true analgesia) or by false positive motor impairment. This dissertation addresses this weakness by complementing cannabinoid effects in conventional assays of pain-stimulated behavior with their effects in novel assays of pain-depressed behavior. Pain-depressed behaviors are defined as behaviors that decrease in rate or intensity following presentation of a noxious stimulus. Motor impairment does not produce false positive
antinociception in assays of pain-depressed behavior, because
antinociception is indicated by a blockade or reversal of pain-induced behavioral depression. In this dissertation, an intraperitoneal (IP) injection of lactic acid served as an acute noxious stimulus to stimulate stretching (pain-stimulated behavior) or depress intracranial self-stimulation (ICSS) (pain-depressed behavior), whereas, IP injection(s) of lipopolysaccharide (LPS) served as a chronic/acute inflammatory-related noxious stimulus to stimulate mechanical allodynia (pain-stimulated behavior) or depress ICSS (pain-depressed behavior). Cannabinoids tested in the assays of acid-stimulated stretching and acid-depressed ICSS included: mixed CB1R/CB2R agonists THC and CP55940, drugs that modulate levels of the endogenous cannabinoid agonist anandamide (URB597 and PF3845), and a selective CB2R agonist, GW405833. THC was also tested in assays of LPS-stimulated mechanical allodynia and LPS-depressed ICSS. In general, mixed CB1R/CB2R agonists were ineffective or exacerbated pain-depressed behavior regardless of noxious stimulus. Contrastingly, URB597 and GW405833 produced
antinociception in the assay of acid-depressed ICSS; however their effects were not mediated by CBRs. All compounds produced
antinociception in the assay of pain-stimulated behavior, except for PF3845. These results suggest that assays of pain-depressed behavior may be useful for development of cannabinoid analgesic medications, but that further research is needed to determine mechanisms underlying cannabinoid-mediated
antinociception in these assays.
Advisors/Committee Members: Sidney Negus.
Subjects/Keywords: rat; antinociception; pain; cannabinoid; behavior; Medical Pharmacology; Medical Sciences; Medicine and Health Sciences
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kwilasz, A. (2013). Effect of cannabinoids on pain-stimulated and pain-depressed behavior in rats. (Doctoral Dissertation). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/SRD1-6Q02 ; https://scholarscompass.vcu.edu/etd/486
Chicago Manual of Style (16th Edition):
Kwilasz, Andrew. “Effect of cannabinoids on pain-stimulated and pain-depressed behavior in rats.” 2013. Doctoral Dissertation, Virginia Commonwealth University. Accessed February 28, 2021.
https://doi.org/10.25772/SRD1-6Q02 ; https://scholarscompass.vcu.edu/etd/486.
MLA Handbook (7th Edition):
Kwilasz, Andrew. “Effect of cannabinoids on pain-stimulated and pain-depressed behavior in rats.” 2013. Web. 28 Feb 2021.
Vancouver:
Kwilasz A. Effect of cannabinoids on pain-stimulated and pain-depressed behavior in rats. [Internet] [Doctoral dissertation]. Virginia Commonwealth University; 2013. [cited 2021 Feb 28].
Available from: https://doi.org/10.25772/SRD1-6Q02 ; https://scholarscompass.vcu.edu/etd/486.
Council of Science Editors:
Kwilasz A. Effect of cannabinoids on pain-stimulated and pain-depressed behavior in rats. [Doctoral Dissertation]. Virginia Commonwealth University; 2013. Available from: https://doi.org/10.25772/SRD1-6Q02 ; https://scholarscompass.vcu.edu/etd/486

University of Tasmania
25.
Paul, AK.
Strategies to reduce the impact of opioid‐induced adverse effects.
Degree: 2018, University of Tasmania
URL: https://eprints.utas.edu.au/28543/1/Paul_whole_thesis.pdf
;
Paul,
AK
ORCID:
0000-0002-6090-2407
<https://orcid.org/0000-0002-6090-2407>
2018
,
'Strategies
to
reduce
the
impact
of
opioid‐induced
adverse
effects',
PhD
thesis,
University
of
Tasmania.
► Development of antinociceptive tolerance in the clinic after repeated administration of morphine limits its chronic use. Despite knowledge about the molecular mechanisms of morphine tolerance,…
(more)
▼ Development of antinociceptive tolerance in the clinic after repeated administration of morphine limits its chronic use. Despite knowledge about the molecular mechanisms of morphine tolerance, we know little about the influence of dosage regimen (starting dose, follow-up dose, dosing and duration of treatment) for its development. I hypothesised that morphine dose, as well as dose increments, contribute to tolerance development. In addition, morphine-induced behavioural changes also might follow a similar pattern of antinociception and tolerance. Four groups of male Sprague Dawley rats received different daily doses of intermittent subcutaneous morphine for 14 days. After the development of antinociceptive tolerance, different increments of morphine doses were administered until tolerance redeveloped. Animals treated with lower starting-doses of morphine developed antinociceptive tolerance faster than those started on higher doses. Higher starting-doses and higher dose-increments after tolerance development resulted in more sustained antinociception and delayed the re-development of tolerance. These results were replicated in two anti-nociceptive assays and were therefore not assay-specific. The kinetics of morphineinduced motor suppression and desensitisation were similar to those of antinociception and antinociceptive-tolerance respectively. Overall, morphine dosing regimen in rats appears to significantly influence antinociceptive tolerance and total antinociception. My results also indicate that repetitive morphine dosing leads to desensitisation of motor suppression in all major motor behavioural parameters and manifests behavioural tolerance in conjunction with antinociceptive tolerance. Therefore, the results highlight that an optimised morphine dosing strategy can delay antinociceptive tolerance and reduce behavioural adverse effects.
Morphine and most other clinical opioids are MOP receptor agonists. The MOP receptor is responsible for both antinociception and generation of antinociceptive tolerance. Previous studies showed that an opioid ligand with mixed activity on multiple opioid receptor can reduce antinociceptive tolerance compared to morphine or other clinical opioids. Several novel opioids synthesised at the University of Tasmania were characterised for their in vitro specificity for major opioid receptors (MOP, DOP, KOP and NOP receptors) before one selected mixed activity opioid was tested for its antinociceptive effect, antinociceptive tolerance and motor behavioural effects in vivo. Collectively, UTA1003 acted as a MOP and KOP receptor agonist and a DOP receptor partial agonist. Therefore, I expected the ligand to reduce tolerance and motor suppression over a repeated treatment regimen. In rats, UTA1003 showed a mild antinociceptive effect with no noticeable motor suppression after subcutaneous administration. After repeated treatment over a period of eight days, UTA1003 displayed no tolerance and no motor behavioural adverse effect. In addition, the ligand maintained approximately 50%…
Subjects/Keywords: antinociception; antinociceptive tolerance; motor behaviour; morphine; mixed-activity opioid; chronic administration; motor suppression; age
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Paul, A. (2018). Strategies to reduce the impact of opioid‐induced adverse effects. (Thesis). University of Tasmania. Retrieved from https://eprints.utas.edu.au/28543/1/Paul_whole_thesis.pdf ; Paul, AK ORCID: 0000-0002-6090-2407 <https://orcid.org/0000-0002-6090-2407> 2018 , 'Strategies to reduce the impact of opioid‐induced adverse effects', PhD thesis, University of Tasmania.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Paul, AK. “Strategies to reduce the impact of opioid‐induced adverse effects.” 2018. Thesis, University of Tasmania. Accessed February 28, 2021.
https://eprints.utas.edu.au/28543/1/Paul_whole_thesis.pdf ; Paul, AK ORCID: 0000-0002-6090-2407 <https://orcid.org/0000-0002-6090-2407> 2018 , 'Strategies to reduce the impact of opioid‐induced adverse effects', PhD thesis, University of Tasmania..
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Paul, AK. “Strategies to reduce the impact of opioid‐induced adverse effects.” 2018. Web. 28 Feb 2021.
Vancouver:
Paul A. Strategies to reduce the impact of opioid‐induced adverse effects. [Internet] [Thesis]. University of Tasmania; 2018. [cited 2021 Feb 28].
Available from: https://eprints.utas.edu.au/28543/1/Paul_whole_thesis.pdf ; Paul, AK ORCID: 0000-0002-6090-2407 <https://orcid.org/0000-0002-6090-2407> 2018 , 'Strategies to reduce the impact of opioid‐induced adverse effects', PhD thesis, University of Tasmania..
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Paul A. Strategies to reduce the impact of opioid‐induced adverse effects. [Thesis]. University of Tasmania; 2018. Available from: https://eprints.utas.edu.au/28543/1/Paul_whole_thesis.pdf ; Paul, AK ORCID: 0000-0002-6090-2407 <https://orcid.org/0000-0002-6090-2407> 2018 , 'Strategies to reduce the impact of opioid‐induced adverse effects', PhD thesis, University of Tasmania.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Guelph
26.
Laniesse, Delphine.
Pharmacology and antinociception of a sustained-released butorphanol – poloxamer 407 formulation in Amazon parrots.
Degree: Associate Diploma in Agriculture, Agriculture, 2016, University of Guelph
URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9674
► Butorphanol is an opioid drug used for pain management in Psittacidae. It has a short duration of action (2-3h) when administered IM or IV. In…
(more)
▼ Butorphanol is an opioid drug used for pain management in Psittacidae. It has a short duration of action (2-3h) when administered IM or IV. In order to decrease frequency of handling and injections, there is a need for a long-acting opioid analgesic in avian medicine. Poloxamer 407 (P407) is a hydrogel commonly used to prepare sustained-release drugs. P407 is liquid when cold and becomes a gel at body temperature. The objective of this study was to evaluate the rheological properties and in vitro diffusion of a formulation of butorphanol in a P407 base (But-P407), as well as its pharmacokinetic parameters and nociceptive effects in Amazon parrots. But-P407 25% (8.3 mg/mL) had in vitro characteristics that made it a good candidate for a sustained-release analgesic medication: it was a gel at avian body temperature, could be sterilized by microfiltration, and its diffusion through a dialysis membrane was slower than that of butorphanol tartrate. Butorphanol was well absorbed from But-P407 25% in Hispaniolan Amazon parrots (Amazona ventralis) (12.5 mg/kg SC), and its pharmacokinetic profile was compatible with a sustained-release drug. Plasma concentrations stayed above the suspected therapeutic threshold for 3-8h. However, no analgesic effect of this formulation could be detected in orange-winged Amazon parrots (Amazona amazonica) (12.5 mg/kg SC) delivered a thermal noxious stimulus. These results could reflect poor analgesic effect of butorphanol, confounding of the poloxamer base, or a lack of sensitivity of the thermal analgesiometric model in this species. Further studies are warranted to provide recommendations for the clinical use of But-P407 25% in birds.
Advisors/Committee Members: Smith, Dale A. (advisor).
Subjects/Keywords: avian; butorphanol; analgesia; poloxamer; P407; pharmacokinetic; pharmacodynamic; nociception; antinociception; rheology; amazon parrot; bird; opioid
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Laniesse, D. (2016). Pharmacology and antinociception of a sustained-released butorphanol – poloxamer 407 formulation in Amazon parrots. (Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9674
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Laniesse, Delphine. “Pharmacology and antinociception of a sustained-released butorphanol – poloxamer 407 formulation in Amazon parrots.” 2016. Thesis, University of Guelph. Accessed February 28, 2021.
https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9674.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Laniesse, Delphine. “Pharmacology and antinociception of a sustained-released butorphanol – poloxamer 407 formulation in Amazon parrots.” 2016. Web. 28 Feb 2021.
Vancouver:
Laniesse D. Pharmacology and antinociception of a sustained-released butorphanol – poloxamer 407 formulation in Amazon parrots. [Internet] [Thesis]. University of Guelph; 2016. [cited 2021 Feb 28].
Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9674.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Laniesse D. Pharmacology and antinociception of a sustained-released butorphanol – poloxamer 407 formulation in Amazon parrots. [Thesis]. University of Guelph; 2016. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9674
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide
27.
Athanasos, Peter.
Opioid maintained subjects and the effects of high dose morphine and adjuvant analgesics.
Degree: 2013, University of Adelaide
URL: http://hdl.handle.net/2440/83272
► Research has shown that maintenance on methadone and buprenorphine for the treatment of opioid addiction can produce the effects of hyperalgesia. This presents difficulties in…
(more)
▼ Research has shown that maintenance on methadone and buprenorphine for the treatment of opioid addiction can produce the effects of hyperalgesia. This presents difficulties in the management of moderate to severe acute pain in this population. The situation is complicated by a dearth of evidence-based guidelines for pain management. The main aims of the four studies described in this thesis were to examine whether very high intravenous morphine doses alone (55.2 mg)(targeting plasma morphine concentrations of 180 ng/ml), or in combination with ketorolac (185.4 mg)(targeting plasma ketorolac concentrations of 4000 ng/ml), tramadol (229 mg)(targeting plasma tramadol concentrations of 1000 ng/ml) or S(+)-Ketamine (S-ketamine) (14.5 mg)(targeting plasma S-ketamine concentrations of 60 ng/ml) (opioid adjuvants) produced
antinociception or respiratory effects in methadone maintained subjects (methadone subjects) and buprenorphine maintained subjects (buprenorphine subjects). The antinociceptive tests of the cold pressor and electrical stimulation were utilised. The effects of different maintenance doses of methadone and buprenorphine were also examined. Methadone maintained subjects were stratified into once daily dose groups of 11-45 (n=6), 46-80 (n=6) and 81-115 (n=6) mg per day. Buprenorphine maintained subjects were stratified into once daily dose groups of 2 to 8 (n=4), 9 to 15 (n=4) and 16-22 (n=4) mg per day. A healthy control group was administered lower doses of morphine alone (11.95 mg), and with adjuvants. The same doses of adjuvants were used in each instance. In the first study high dose morphine failed to provide
antinociception for the methadone subjects. High dose morphine significantly decreased respiration rate, but only by an average of 2 breaths per minute. Methadone subjects were hyperalgesic in the cold pressor test. There were no differences in the antinociceptive responses of the different stratified methadone groups to the high dose morphine. Methadone subjects maintained on the highest doses had the highest respiratory depression. In the second study buprenorphine subjects performed similarly to methadone subjects in at least three respects: firstly, high dose morphine had little antinociceptive effect; secondly, this dose significantly decreased respiration rate; and thirdly, buprenorphine and methadone subjects were similarly hyperalgesic in the cold pressor test. There were also no differences in the antinociceptive responses of the different buprenorphine groups to the high dose morphine. In the third study tramadol and ketorolac, when combined with high dose morphine, failed to provide
antinociception in either the cold pressor or electrical stimulation tests to methadone subjects. The combination of S-ketamine and high dose morphine provided statistically but not clinically significant improvement in
antinociception in the cold pressor test. In the fourth study ketorolac and high dose morphine did not provide
antinociception in buprenorphine maintained subjects. While the combinations of…
Advisors/Committee Members: White, Jason Mark (advisor), Somogyi, Andrew Alexander (advisor), Bochner, Felix (advisor), School of Medical Sciences (school).
Subjects/Keywords: methadone; buprenorphine; plasma morphine; antinociception; hyperalgesia; cold pressor test; tramadol; ketorolac S ketamine
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APA ·
Chicago ·
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APA (6th Edition):
Athanasos, P. (2013). Opioid maintained subjects and the effects of high dose morphine and adjuvant analgesics. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/83272
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Athanasos, Peter. “Opioid maintained subjects and the effects of high dose morphine and adjuvant analgesics.” 2013. Thesis, University of Adelaide. Accessed February 28, 2021.
http://hdl.handle.net/2440/83272.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Athanasos, Peter. “Opioid maintained subjects and the effects of high dose morphine and adjuvant analgesics.” 2013. Web. 28 Feb 2021.
Vancouver:
Athanasos P. Opioid maintained subjects and the effects of high dose morphine and adjuvant analgesics. [Internet] [Thesis]. University of Adelaide; 2013. [cited 2021 Feb 28].
Available from: http://hdl.handle.net/2440/83272.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Athanasos P. Opioid maintained subjects and the effects of high dose morphine and adjuvant analgesics. [Thesis]. University of Adelaide; 2013. Available from: http://hdl.handle.net/2440/83272
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Northeastern University
28.
Chopda, Girish Rajmal.
Cannabinoid mediated diuresis in mice.
Degree: PhD, School of Pharmacy, 2014, Northeastern University
URL: http://hdl.handle.net/2047/D20196364
► Cannabinoid receptor agonists increase urinary output in rats; however these effects have not been characterized in mice. This study investigates whether diuresis is a cannabinoid…
(more)
▼ Cannabinoid receptor agonists increase urinary output in rats; however these effects have not been characterized in mice. This study investigates whether diuresis is a cannabinoid receptor mediated effect in mice, and further compares cannabinoid mediated diuresis with antinociception. Adult male CD1 mice were injected sc (10 ml/kg) with vehicle or novel and commercially available cannabinoid agonists [AM4054, AM7418, THC (Δ9-tetrahydrocannabinol) and WIN55212-22]. Voided urine was measured over 6 hr using single dosing procedures. Antinociception was measured using cumulative dosing procedures and a warm water (52°C) tail-withdrawal assay. In antagonism studies, cannabinoid CB1 receptor selective antagonist rimonabant (0.1-10.0 mg/kg), peripherally restricted cannabinoid CB1 receptor antagonist AM6545 (1.0-10.0 mg/kg) or cannabinoid CB2 receptor selective antagonist AM630 (0.1-10.0 mg/kg) were administered as a 30min pretreatment. All of the cannabinoid agonists increased diuresis, yielding biphasic dose response curves with maximum voided urine ranging from 28-35 g/kg; urine output after vehicle injection ranged from 7-15 g/kg. All cannabinoid agonists also increased analgesia dose-dependently with peak effects similar to morphine. Peak diuretic effects occurred at doses approximately ½ log unit lower than those that produced maximum antinociceptive effects. Rimonabant dose dependently shifted the diuretic and antinociceptive dose response curve of AM4054 to the right, and was marginally more potent in the diuresis assay. Repeated administration of THC resulted in tolerance to the diuretic and antinociceptive effects of cannabinoids, which was accompanied by CB1 receptor downregulation. Our results indicate that cannabinoid agonists produce increases in urine output by actions at central CB1 receptors and decreases in urine output by actions at both central and peripheral CB1 receptors.
Subjects/Keywords: antinociception; cannabinoid; Cannabinoids; Agonists; Therapeutic use; Cannabinoids; Receptors; Therapeutic use; Diuresis; Rimonabant; Therapeutic use
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chopda, G. R. (2014). Cannabinoid mediated diuresis in mice. (Doctoral Dissertation). Northeastern University. Retrieved from http://hdl.handle.net/2047/D20196364
Chicago Manual of Style (16th Edition):
Chopda, Girish Rajmal. “Cannabinoid mediated diuresis in mice.” 2014. Doctoral Dissertation, Northeastern University. Accessed February 28, 2021.
http://hdl.handle.net/2047/D20196364.
MLA Handbook (7th Edition):
Chopda, Girish Rajmal. “Cannabinoid mediated diuresis in mice.” 2014. Web. 28 Feb 2021.
Vancouver:
Chopda GR. Cannabinoid mediated diuresis in mice. [Internet] [Doctoral dissertation]. Northeastern University; 2014. [cited 2021 Feb 28].
Available from: http://hdl.handle.net/2047/D20196364.
Council of Science Editors:
Chopda GR. Cannabinoid mediated diuresis in mice. [Doctoral Dissertation]. Northeastern University; 2014. Available from: http://hdl.handle.net/2047/D20196364

University of Georgia
29.
Rahn, Elizabeth Jocelyn.
Activation of cannabinoid CB2 receptors suppresses chemotherapy-induced neuropathy in rats.
Degree: 2014, University of Georgia
URL: http://hdl.handle.net/10724/26756
► The cannabinoid system is a recently discovered neurotransmitter system that shares the same pharmacological target as the primary active constituent in cannabis, 9-tetrahydrocannabinol. The cannabinoid…
(more)
▼ The cannabinoid system is a recently discovered neurotransmitter system that shares the same pharmacological target as the primary active constituent in cannabis, 9-tetrahydrocannabinol. The cannabinoid system consists of two primary
endogenous neurotransmitters (anandamide and 2-arachidonoylglycerol) as well as at least two metabotropic receptors (CB1 and CB2). Activation of the CB1 receptor is associated with psychotropic and motor effects, whereas activation of the CB2 receptor
lacks these central nervous system side effects. The cannabinoid receptors have disparate distributions in the body, which may account for their differential side effect profiles. The CB1 receptor is localized primarily within the central nervous system
(CNS). The CB2 receptor was originally believed to be restricted to immune cells in the periphery; however recent suggests indicates the presence of this receptor at low levels within the CNS. The present studies focus on the cannabinoid CB2 receptor as
a potential target for novel analgesics. Antinociceptive properties of the purported cannabinoid CB2 receptor agonists, (R,S)-AM1241, (R)-AM1241, (S)-AM1241, AM1714, and AM1710 were assessed in response to both mechanical and thermal stimulation to
better characterize these drugs. All four drugs produced robust antinociception in response to thermal, but not mechanical stimulation. The antinociceptive profile of AM1714 and at high doses, AM1710, involved activation of the cannabinoid CB1 receptor,
whereas effects of (R,S)-AM1241 and its enantiomers were mediated exclusively by the cannabinoid CB2 receptor. (R,S)-AM1241, AM1714, and AM1710 failed to show CNS side effects at doses that produced robust antinociception to thermal stimulation. The
final series of experiments assessed the efficacy of cannabinoid CB2-preferring agonists in a model of chemotherapy-induced neuropathy. (R,S)-AM1241, (R)-AM1241, and AM1714 attenuated established mechanical allodynia observed in animals treated with the
chemotherapeutic agent paclitaxel. Prophylactic administration of the CB2-preferring agonist, AM1710, the mixed cannabinoid CB1/CB2 agonist, WIN55,212-2, and the neuropathic pain medication, gabapentin, suppressed the development of paclitaxel-induced
neuropathic nociception with equal efficacy. All three drugs produced a protective effect against the development of neuropathy that was present up to two weeks following removal of the drug. Collectively, the data presented herein suggests that the
cannabinoid CB2 receptor is a viable pharmacological target with immense potential for analgesic development with limited adverse side effects.
Subjects/Keywords: Antinociception; cannabinoid; cancer; CB1; CB2; chemotherapy; cold allodynia; mechanical allodynia; naloxone; neuropathic pain; opioid; tetrad
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Rahn, E. J. (2014). Activation of cannabinoid CB2 receptors suppresses chemotherapy-induced neuropathy in rats. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/26756
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Rahn, Elizabeth Jocelyn. “Activation of cannabinoid CB2 receptors suppresses chemotherapy-induced neuropathy in rats.” 2014. Thesis, University of Georgia. Accessed February 28, 2021.
http://hdl.handle.net/10724/26756.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Rahn, Elizabeth Jocelyn. “Activation of cannabinoid CB2 receptors suppresses chemotherapy-induced neuropathy in rats.” 2014. Web. 28 Feb 2021.
Vancouver:
Rahn EJ. Activation of cannabinoid CB2 receptors suppresses chemotherapy-induced neuropathy in rats. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Feb 28].
Available from: http://hdl.handle.net/10724/26756.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Rahn EJ. Activation of cannabinoid CB2 receptors suppresses chemotherapy-induced neuropathy in rats. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/26756
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Kentucky
30.
Dhooper, Harpreet Kaur.
OPIOID-CANNABINOID CODRUGS WITH ENHANCED ANALGESIC AND PHARMACOKINETIC PROFILE.
Degree: 2010, University of Kentucky
URL: https://uknowledge.uky.edu/gradschool_diss/98
► The central hypothesis of the dissertation is that “the design and synthesis of a codrug of an opiate and a cannabinoid can be achieved which…
(more)
▼ The central hypothesis of the dissertation is that “the design and synthesis of a codrug of an opiate and a cannabinoid can be achieved which is stable in the gastrointestinal tract and shows a superior pharmacological and pharmacokinetic profile when compared to a physical mixture of the two parent drugs.” To prove the hypothesis, a series of novel codrugs were prepared by conjugation of the opiate drug codeine with Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol, abn-cannabidiol and an opiate prodrug 3-O-acetylmorphine with Δ9-THC. Codeine-cannabinoid codrugs were evaluated for analgesic activity in the rat after oral administration. The Cod-THC codrug showed greater effectiveness as well as prolonged pain management properties as compared to the parent drugs. The stability of Cod-THC codrug in aqueous solutions from pH 1-9, in simulated gastrointestinal fluids, in brain homogenate and the hydrolysis of the carbonate ester linkage in rat plasma suggested that after oral administration, the codrug would be absorbed intact from the GI tract and then hydrolyze in the plasma to generate both parent drugs. The enzymes present in rat brain homogenate were incapable of cleaving the codrug into the parent drugs.
The pharmacokinetic profiles of the Cod-THC codrug and an equimolar physical mixture of the parent drugs were evaluated in rats. The plasma concentrations of codeine and Δ9-THC were much higher after codrug administration compared to the plasma concentrations of these drugs after oral administration of an equimolar physical mixture. The parent drugs were also present in the plasma for longer period of time compared to the physical mixture, probably due to the sustained release of the parent drugs from codrug in the plasma. The concentrations of codeine and Δ9-THC were much higher in rat brain after oral administration of the Cod-THC codrug as compared to brain concentrations of these drugs after oral administration of the physical mixture. Thus, the design and synthesis of an opiate and a cannabinoid codrug was achieved which was stable in the gastrointestinal tract, showed enhanced analgesic effects as compared to the parent drugs, and also showed a superior pharmacokinetic profile when compared to a physical mixture or the two parent drugs.
Subjects/Keywords: Opioid; Cannabinoid; Codrug; Antinociception; Pharmacokinetics; Chemistry
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Dhooper, H. K. (2010). OPIOID-CANNABINOID CODRUGS WITH ENHANCED ANALGESIC AND PHARMACOKINETIC PROFILE. (Doctoral Dissertation). University of Kentucky. Retrieved from https://uknowledge.uky.edu/gradschool_diss/98
Chicago Manual of Style (16th Edition):
Dhooper, Harpreet Kaur. “OPIOID-CANNABINOID CODRUGS WITH ENHANCED ANALGESIC AND PHARMACOKINETIC PROFILE.” 2010. Doctoral Dissertation, University of Kentucky. Accessed February 28, 2021.
https://uknowledge.uky.edu/gradschool_diss/98.
MLA Handbook (7th Edition):
Dhooper, Harpreet Kaur. “OPIOID-CANNABINOID CODRUGS WITH ENHANCED ANALGESIC AND PHARMACOKINETIC PROFILE.” 2010. Web. 28 Feb 2021.
Vancouver:
Dhooper HK. OPIOID-CANNABINOID CODRUGS WITH ENHANCED ANALGESIC AND PHARMACOKINETIC PROFILE. [Internet] [Doctoral dissertation]. University of Kentucky; 2010. [cited 2021 Feb 28].
Available from: https://uknowledge.uky.edu/gradschool_diss/98.
Council of Science Editors:
Dhooper HK. OPIOID-CANNABINOID CODRUGS WITH ENHANCED ANALGESIC AND PHARMACOKINETIC PROFILE. [Doctoral Dissertation]. University of Kentucky; 2010. Available from: https://uknowledge.uky.edu/gradschool_diss/98
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