title: Substitution and primary dependence studies in animals.
abstract: The mixed agonist-antagonist analgesics buprenorphine, butorphanol, nalbuphine, pentazocine and picenadol were compared to the prototype mu and kappa agonists morphine and Mr 2033, respectively, in the following tests in rhesus monkeys: overt behavioral effects upon acute administration in drug-naive animals; discriminative stimulus properties in monkeys trained to respond to either etorphine or ethylketazocine; self-administration of the test agent relative to codeine; single dose suppression and precipitation in withdrawn and non-withdrawn morphine-dependent monkeys, respectively; and primary addiction studies in drug-naive animals. Whereas both buprenorphine and nalbuphine precipitate withdrawal in morphine-dependent monkeys, withdrawal following chronic administration of buprenorphine resulted in no observable signs of abstinence, while nalbuphine withdrawal was similar to that seen in morphine-dependent monkeys. Butorphanol, pentazocine and picenadol all produced mild dependence of the kappa-type; that is, natural withdrawal behavior similar to that seen following chronic Mr 2033 administration.
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001575:Benzomorphans / Q000494:pharmacology; D002047:Buprenorphine / Q000494:pharmacology; D002077:Butorphanol / Q000494:pharmacology; D003061:Codeine / Q000494:pharmacology; D004192:Discrimination, Psychological; D006801:Humans; D008253:Macaca mulatta; D009019:Morphinans / Q000494:pharmacology*; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009021:Morphine Dependence / Q000188:drug therapy; D009266:Nalbuphine / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010423:Pentazocine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000139:chemically induced
chemical_list: D001575:Benzomorphans; D009019:Morphinans; D009292:Narcotic Antagonists; D010880:Piperidines; D002047:Buprenorphine; C032478:MR 2034; D009020:Morphine; D009266:Nalbuphine; D002077:Butorphanol; D010423:Pentazocine; C035115:picenadol; D003061:Codeine