Characterization of prototypical opioid antagonists, agonist-antagonists, and agonists in the morphine-dependent rhesus monkey.
In non-withdrawn maximally-dependent rhesus monkeys, both naloxone (NOX) and nalorphine (NAL) precipitated withdrawal when given 2 h after morphine (M). When these drugs were given 15 h after M, at which time the animals were in severe withdrawal and M blood levels were much lower, they promptly exacerbated withdrawal. Thus, mu antagonists may act competitively in non-withdrawn addicts and noncompetitively in withdrawn subjects. Buprenorphine (BRN), the partial mu agonist, precipitated withdrawal in stable addicts and partly suppressed withdrawal signs in abstinent addicts. Finally, ethyl-ketocyclazocine (EKC), the purported kappa agonist, did not precipitate but partly suppressed withdrawal at doses producing severe side effects. Perhaps this suppression is associated with kappa activity.
D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D016314:Ethylketocyclazocine; D006801:Humans; D008253:Macaca mulatta; D009021:Morphine Dependence / Q000209:etiology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects; D017450:Receptors, Opioid, mu; D013375:Substance Withdrawal Syndrome / Q000209:etiology
D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone; D002047:Buprenorphine; D016314:Ethylketocyclazocine; D003496:Cyclazocine