title: Stereospecific inhibition of oxotremorine-induced antinociception by (+)-isomers of opioid antagonists: comparison with opioid receptor agonists.
abstract: The antagonistic effects of the two benzomorphan opioid antagonists, Mr-1452 and Mr-2266 and their respective (+)-isomers Mr-1453 and Mr-2267 upon morphine, ethylketocyclazocine (EKC), D-ala2-D-leu5-enkephalinamide (BW 180-C) and oxotremorine (OTMN) antinociceptive activity in mice were investigated. Pretreatment with either Mr-1452 (2.0 mg Kg-1 i.p.) or Mr-2266 (2.0 mg kg-1 i.p.) significantly antagonized the antinociceptive effects of the three opioid agonists in the hot plate test, but were ineffective against OTMN, which in contrast was antagonized by the (+)-isomers. Interaction between the antagonists and submaximal analgesic doses of the opioids or OTMN produced similar results in the tail immersion assay. However, the effect of Mr-2267 on OTMN was biphasic and this contrasted with Mr-1453 which produced consistent and graded antagonism.
mesh_terms: D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D016314:Ethylketocyclazocine; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D010095:Oxotremorine / Q000037:antagonists & inhibitors*; D011957:Receptors, Opioid / Q000187:drug effects; D013237:Stereoisomerism
chemical_list: D001575:Benzomorphans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D010095:Oxotremorine; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine; D003496:Cyclazocine