Characterization of prototypical opioid antagonists, agonist-antagonists, and agonists in the morphine-dependent...

In non-withdrawn maximally-dependent rhesus monkeys, both naloxone (NOX) and nalorphine (NAL) precipitated withdrawal when given 2 h after morphine (M).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 Thus, mu antagonists may act competitively in non-withdrawn addicts and noncompetitively in withdrawn subjects.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.