Glick S D, Visker K E, Maisonneuve I M
Department of Pharmacology and Neuroscience, Albany Medical College, NY 12208, USA.
Eur J Pharmacol. 1998 Sep 11;357(1):9-14. doi: 10.1016/s0014-2999(98)00548-2.
Cyclazocine is a kappa-opioid receptor agonist and mu-opioid receptor antagonist that was studied in the 1960s as a potential treatment for heroin addicts. Based on the evidence that opioid mechanisms modulate the reinforcing effects of cocaine, it has been suggested that cyclazocine be reconsidered for use in treating cocaine dependence. In the present study, the effects of orally administered (+/-)-cyclazocine, (+)-cyclazocine and (-)-cyclazocine on intravenous cocaine self-administration were assessed in rats. (+/-)-Cyclazocine produced a dose-related (2-8 mg/kg) decrease in cocaine intake without affecting bar-press responding for water. Neither enantiomer significantly altered responding for either cocaine or water. The efficacy of orally administered (+/-)-cyclazocine on cocaine self-administration was comparable to that previously observed using the intraperitoneal route. Distinct actions of the enantiomers of cyclazocine that might contribute to the unique efficacy of the racemate are discussed. Although the mechanistic basis for the results are not entirely understood, the data suggest that (+/-)-cyclazocine should be considered as a potential treatment for cocaine dependence.
环唑辛是一种κ-阿片受体激动剂和μ-阿片受体拮抗剂，在20世纪60年代被作为海洛因成瘾者的一种潜在治疗方法进行研究。基于阿片类机制调节可卡因强化作用的证据，有人建议重新考虑将环唑辛用于治疗可卡因依赖。在本研究中，评估了口服（±）-环唑辛、（+）-环唑辛和（-）-环唑辛对大鼠静脉注射可卡因自我给药的影响。（±）-环唑辛使可卡因摄入量呈剂量相关（2-8毫克/千克）减少，而不影响对水的压杆反应。两种对映体均未显著改变对可卡因或水的反应。口服（±）-环唑辛对可卡因自我给药的疗效与先前经腹腔途径观察到的疗效相当。讨论了环唑辛对映体可能导致外消旋体独特疗效的不同作用。尽管结果的机制基础尚未完全理解，但数据表明（±）-环唑辛应被视为治疗可卡因依赖的一种潜在方法。
