Sziráki I, Kardos V, Patthy M, Pátfalusi M, Gaál J, Solti M, Kollár E, Singer J
Institute for Drug Research, Budapest, Hungary.
J Neural Transm Suppl. 1994;41:207-19. doi: 10.1007/978-3-7091-9324-2_27.
The ability of 1-deprenyl to protect against the parkinsonian effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been attributed to the inhibition of conversion of MPTP to MPP+ (1-methyl-4-phenylpyridinium) catalyzed by MAO-B. We report here that deprenyl-treatment in mice has an additional neuroprotective element associated with the rapid metabolization of 1-deprenyl to 1-methamphetamine and 1-amphetamine. 1-Methamphetamine and 1-amphetamine inhibit MPP(+)-uptake into striatal synaptosomes prepared from rats. Post-treatment by 1-deprenyl, 1-methamphetamine, 1-amphetamine (at times when MPTP is no longer present in the striatum of mice) protects against neurotoxicity in C57BL mice by blocking the uptake of MPP+ into dopaminergic neurons, and even against the neurotoxicity induced by 2'CH3-MPTP, which is partly bioactivated by MAO-A. These findings may have clinical implications since deprenyl has recently been found to delay the progression of Parkinson's disease.
司来吉兰预防1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）所致帕金森效应的能力归因于其对单胺氧化酶B（MAO-B）催化的MPTP向1-甲基-4-苯基吡啶离子（MPP+）转化的抑制作用。我们在此报告，小鼠经司来吉兰治疗还有另一种神经保护作用，这与司来吉兰快速代谢为1-甲基苯丙胺和1-苯丙胺有关。1-甲基苯丙胺和1-苯丙胺可抑制MPP+摄取到从大鼠制备的纹状体突触体中。在小鼠纹状体中MPTP已不存在时，用司来吉兰、1-甲基苯丙胺、1-苯丙胺进行后期治疗，可通过阻断MPP+摄取到多巴胺能神经元中，甚至预防由2'-甲基-MPTP诱导的神经毒性，2'-甲基-MPTP部分由MAO-A进行生物活化。这些发现可能具有临床意义，因为最近发现司来吉兰可延缓帕金森病的进展。
