Nickel B, Szelenyi I, Schulze G
Department of Pharmacology, ASTA Medica AG, Frankfurt/Main, Germany.
Clin Pharmacol Ther. 1994 Dec;56(6 Pt 2):757-67. doi: 10.1038/clpt.1994.206.
l-Deprenyl is a useful drug that has been successful in the clinical treatment of parkinsonism. However, l-deprenyl is a phenylalkylamine derivative that undergoes metabolic transformation to l-methamphetamine and l-amphetamine. Therefore, the question arises whether l-deprenyl possesses amphetamine-like abuse liability. This article reviews a series of different preclinical studies in rats that used experimental procedures to provide preclinical information predictive of human abuse liability. In one series we investigated whether repeated administration of l-deprenyl to rats resulted in observable signs of physical dependence. In a second series of studies, the effects of l-deprenyl on the cortical electrical activity of freely moving rats were investigated. Finally, the influence of l-deprenyl on behavior of the animals was studied. In all studies, different stereospecific configurations of amphetamine and deprenyl were compared. During and after 6 weeks of oral administration of l-deprenyl, no signs of physical dependence were observed in rats after withdrawal of the drug. In contrast, with d-deprenyl, d-amphetamine, and racemic d,l-amphetamine, signs indicative of physical dependence were observed after withdrawal of the drug. For example, the body weight of the rats was increased. In addition, changes in electroencephalograms and behavior of rats induced by l-deprenyl and l-amphetamine were different from those produced by the d-enantiomers. Thus preclinical results confirm the clinical experience that therapeutically relevant doses of l-deprenyl are without physical dependence liability.
左旋司来吉兰是一种有效的药物，已成功用于帕金森病的临床治疗。然而，左旋司来吉兰是一种苯基烷基胺衍生物，会代谢转化为l-甲基苯丙胺和l-苯丙胺。因此，就产生了左旋司来吉兰是否具有类似苯丙胺的滥用可能性这一问题。本文综述了一系列在大鼠身上进行的不同临床前研究，这些研究采用实验程序来提供预测人类滥用可能性的临床前信息。在一系列研究中，我们调查了对大鼠重复给药左旋司来吉兰是否会导致可观察到的身体依赖性迹象。在第二系列研究中，研究了左旋司来吉兰对自由活动大鼠皮层电活动的影响。最后，研究了左旋司来吉兰对动物行为的影响。在所有研究中，都比较了苯丙胺和司来吉兰不同的立体特异性构型。在口服左旋司来吉兰6周期间及之后，停药后大鼠未观察到身体依赖性迹象。相比之下，对于右旋司来吉兰、右旋苯丙胺和消旋d，l-苯丙胺，停药后观察到了身体依赖性迹象。例如，大鼠体重增加。此外，左旋司来吉兰和左旋苯丙胺引起的大鼠脑电图和行为变化与右旋对映体产生的变化不同。因此，临床前结果证实了临床经验，即治疗相关剂量的左旋司来吉兰没有身体依赖性风险。
