Hui F W, Sun C L, Hanig J P
Neurobehav Toxicol Teratol. 1985 Sep-Oct;7(5):443-7.
Anecdotal reports of polydrug abuse in humans using tripelennamine and pentazocine prompted our investigation of drug interactions between tripelennamine, morphine and various synthetic mixed agonist-antagonists in mice. Pentazocine, nalbuphene and butorphanol, at doses of 4.0-8.0 mg/kg, all showed frank or borderline intrinsic antinociceptive activity and potentiated the tripelennamine response, whereas cyclazocine, an experimental compound with very strong mixed agonist-antagonist qualities at 5.0 mg/kg, showed intrinsic antinociceptive activity but was not potentiated by tripelennamine and actually blocked the tripelennamine response. In a comparative study, pentazocine, butorphanol and nalbuphene had no effect on morphine antinociception whereas cyclazocine completely abolished the antinociceptive effects of morphine. Cimetidine blocked the response of cyclazocine, but not nalbuphene, pentazocine or butorphanol. Our findings demonstrate that the mechanism of action of cyclazocine is significantly different from that of the other mixed agonist-antagonists studied. They also suggest possible histaminergic involvement in antinociception, as well as a locus for antinociception separate from the opiate receptor.
关于人类使用曲吡那敏和喷他佐辛后多药滥用的轶事报道促使我们研究曲吡那敏、吗啡与各种合成混合激动剂-拮抗剂在小鼠体内的药物相互作用。喷他佐辛、纳布啡和布托啡诺，剂量为4.0-8.0mg/kg时，均表现出明显或临界的内在抗伤害感受活性，并增强了曲吡那敏的反应，而环唑辛，一种在5.0mg/kg时具有非常强的混合激动剂-拮抗剂特性的实验化合物，表现出内在抗伤害感受活性，但未被曲吡那敏增强，实际上还阻断了曲吡那敏的反应。在一项比较研究中，喷他佐辛、布托啡诺和纳布啡对吗啡的抗伤害感受没有影响，而环唑辛完全消除了吗啡的抗伤害感受作用。西咪替丁阻断了环唑辛的反应，但未阻断纳布啡、喷他佐辛或布托啡诺的反应。我们的研究结果表明，环唑辛的作用机制与所研究的其他混合激动剂-拮抗剂有显著差异。它们还提示组胺能可能参与抗伤害感受，以及存在一个与阿片受体分开的抗伤害感受位点。
