Evidence for a Selective Role of the δ-Opioid Agonist [8R-(4bS*,8aα,8aβ,12bβ)]7,10-Dimethyl-1-methoxy-11-(2-methylpropyl)oxycarbonyl 5,6,7,8,12,12b-hexahydro-(9H)-4,8-methanobenzofuro[3,2-e]pyrrolo[2,3-g]isoquinoline Hydrochloride (SB-235863) in Blocking Hyperalgesia Associated with Inflammatory and Neuropathic Pain Responses
| العنوان: | Evidence for a Selective Role of the δ-Opioid Agonist [8R-(4bS*,8aα,8aβ,12bβ)]7,10-Dimethyl-1-methoxy-11-(2-methylpropyl)oxycarbonyl 5,6,7,8,12,12b-hexahydro-(9H)-4,8-methanobenzofuro[3,2-e]pyrrolo[2,3-g]isoquinoline Hydrochloride (SB-235863) in Blocking Hyperalgesia Associated with Inflammatory and Neuropathic Pain Responses |
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| المؤلفون: | Paola Petrillo, Ottorino Pozzi, Giuseppe Petrone, Ornella Angelici, Tania O. Stean, M. Sbacchi, Guillio M. Dondio, Sharon Bingham, Giovanna Ficalora, Paola Zaratin, Martine Garnier, Mark A. Scheideler, Neil Upton |
| المصدر: | Journal of Pharmacology and Experimental Therapeutics. 307:1079-1089 |
| بيانات النشر: | American Society for Pharmacology & Experimental Therapeutics (ASPET), 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | Male, Narcotics, Agonist, medicine.drug_class, Convulsants, Pharmacology, Carrageenan, Transfection, Binding, Competitive, Rats, Sprague-Dawley, Genes, Reporter, Seizures, Naltrindole, Receptors, Opioid, delta, Cyclic AMP, medicine, Animals, Gastrointestinal Transit, Luciferases, Receptor, Postural Balance, Cells, Cultured, Injections, Intraventricular, Inflammation, Electroshock, Morphine Derivatives, Chemistry, Antagonist, Peripheral Nervous System Diseases, Biological activity, Enzymes, Rats, Nociception, Opioid, Hyperalgesia, Pentylenetetrazole, Molecular Medicine, Sciatic Neuropathy, medicine.symptom, medicine.drug |
| الوصف: | The specific involvement of the delta-opioid receptor in the control of nociception was explored by investigating the pharmacological activity in vivo of a selective, orally active, and centrally penetrant delta-opioid agonist. [8R-(4bS*,8aalpha,8abeta,12bbeta)]7,10-dimethyl-1-methoxy-11-(2-methylpropyl)oxycarbonyl 5,6,7,8,12,12b-hexahydro-(9H)-4,8-methanobenzofuro[3,2-e]pyrrolo[2,3-g]isoquinoline hydrochloride (SB-235863) is a new pyrrolomorphinan with high affinity (Ki = 4.81 +/- 0.39 nM) for the delta-opioid receptor, full agonist activity, and binding selectivity versus the mu- and kappa-opioid receptors of 189-fold and 52-fold, respectively. Perorally administered SB-236863 was inactive in the rat tail-flick and hot-plate tests of acute pain response, but potently reversed thermal hyperalgesia in rats resulting from a carrageenan-induced inflammatory response. This activity could be blocked by the delta-opioid antagonist naltrindole (3 mg/kg s.c.), but selective mu- and kappa-opioid antagonists were ineffective. Naltrindole (1 microg i.c.v.) also blocked the activity of 10 mg/kg (p.o.) SB-235863, showing that the compound activates delta-opioid receptor sites in the central nervous system. SB-235863 was additionally effective at reversing chronic hyperalgesia in the Seltzer rat model of partial sciatic nerve ligation after peroral administration. These data show that the delta-opioid receptor plays a selective role in regulating evoked and lasting changes in nociceptive pain signaling. Classical side effects of mu- and kappa-opioid receptor activation (slowing of gastrointestinal transit and motor incoordination, respectively) were not observed after administration of 70 mg/kg (p.o.) SB-235863, nor was evoked seizure activity affected. These results suggest a selective and limited role of delta-opioid receptors in the modulation of nociception. |
| تدمد: | 1521-0103 0022-3565 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::10f5d36c3c1d84d248a4431fb74bcf24 https://doi.org/10.1124/jpet.103.055590 |
| رقم الأكسشن: | edsair.doi.dedup.....10f5d36c3c1d84d248a4431fb74bcf24 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15210103 00223565 |
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