Carrera M R, Ashley J A, Parsons L H, Wirsching P, Koob G F, Janda K D
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Nature. 1995 Dec 14;378(6558):727-30. doi: 10.1038/378727a0.
Cocaine is a powerfully addictive substance and new strategies are needed to treat its abuse. Generating an active immunization to cocaine offers a means of blocking the actions of the drug by preventing it from entering the central nervous system, and should have fewer side effects than treatments based on manipulation of central neurotransmitter function. The design and preparation of a cocaine immunogen requires special regard for the stability of cocaine both free and as a haptenic determinant. Immunochemistry and a well defined behavioural model were brought together to address the problem of inactivation of the psychostimulant actions of cocaine. We report here that active immunization with a new, stable cocaine conjugate suppressed locomotor activity and stereotyped behaviour in rats induced by cocaine but not by amphetamine. Moreover, following acute injection of cocaine, levels of cocaine in the striatum and cerebellum of the immunized animals were lower than those of control animals. These results suggest that immunopharmacotherapy may be a promising means by which to explore new treatments for cocaine abuse.
可卡因是一种极易成瘾的物质,需要新的策略来治疗其滥用问题。对可卡因进行主动免疫提供了一种通过阻止药物进入中枢神经系统来阻断其作用的方法,并且与基于操纵中枢神经递质功能的治疗方法相比,副作用应该更少。可卡因免疫原的设计和制备需要特别考虑游离可卡因和作为半抗原决定簇的可卡因的稳定性。免疫化学和明确的行为模型相结合,以解决可卡因精神刺激作用失活的问题。我们在此报告,用一种新的、稳定的可卡因缀合物进行主动免疫可抑制可卡因而非苯丙胺诱导的大鼠的运动活动和刻板行为。此外,在急性注射可卡因后,免疫动物纹状体和小脑中的可卡因水平低于对照动物。这些结果表明,免疫药物疗法可能是探索可卡因滥用新治疗方法的一种有前景的手段。