Woods J H, Gmerek D E
Drug Alcohol Depend. 1985 Feb;14(3-4):233-47. doi: 10.1016/0376-8716(85)90059-6.
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self-administration of the test agent relative to codeine; single dose suppression and precipitation in withdrawn and non-withdrawn morphine-dependent monkeys, respectively; and primary addiction studies in drug-naive animals.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.
在恒河猴身上进行的以下试验中，将混合激动剂-拮抗剂镇痛药丁丙诺啡、布托啡诺、纳布啡、喷他佐辛和匹西那多分别与典型的μ和κ激动剂吗啡和Mr 2033进行了比较：对未接触过药物的动物急性给药后的明显行为效应；对经训练对埃托啡或依托卡宗产生反应的猴子的辨别刺激特性；相对于可待因的受试药物的自我给药；分别在戒断和未戒断的吗啡依赖猴子中的单剂量抑制和戒断反应；以及对未接触过药物的动物进行的原发性成瘾研究。虽然丁丙诺啡和纳布啡都会使吗啡依赖的猴子出现戒断反应，但长期给予丁丙诺啡后的戒断反应未观察到明显的戒断迹象，而纳布啡的戒断反应与吗啡依赖猴子的相似。布托啡诺、喷他佐辛和匹西那多均产生轻度的κ型依赖性；也就是说，自然戒断行为类似于长期给予Mr 2033后的情况。
