Magyar K, Szende B, Lengyel J, Tekes K
Department of Pharmacodynamics, Semmelweis University of Medicine, Budapest, Hungary.
J Neural Transm Suppl. 1996;48:29-43. doi: 10.1007/978-3-7091-7494-4_4.
(-)-deprenyl cannot be considered as a simple, selective inhibitor of MAO-B. It increases the dopaminergic tone in the central nervous system by a complex mechanism. The MAO-B inhibition could result in a potentiation of the effect and the reduction of the dose of L-dopa, including the restoration of the sensitivity to L-dopa treatment, when the response to the drug has already been diminished or lost. Pre-treatment with (-)-deprenyl prevent the effect of neurotoxins like MPTP, 6-hydroxydopamine, DSP-4, AF64A by inhibiting the conversion of the pretoxin to toxin, or by inhibiting the neuronal reuptake mechanisms, or the combination of the two processes. However, other effects of the inhibitor cannot be ruled out. (-)-deprenyl, but not its (+)-enantiomer, proved to be a potent inhibitor of programmed cell death (apoptosis) of PC12 cells and that of human melanoma cells, in a concentration which does not induce MAO-B inhibition. The activity of MAO-B increases with age and the age related changes led to an overproduction of neurotoxic agents. The inhibition of the enzyme activity can play a preventive role against neurodegenerative brain disorders. The most widely used MAO-B inhibitor in the therapy is (-)-deprenyl and it lacks the "cheese reaction". The complex mechanism for the lack of the former effect is not fully known.
（-）-司来吉兰不能被视为一种简单的、选择性的单胺氧化酶B（MAO-B）抑制剂。它通过一种复杂的机制增加中枢神经系统中的多巴胺能张力。MAO-B抑制作用可能会增强左旋多巴的效果并降低其剂量，包括当对该药物的反应已经减弱或丧失时恢复对左旋多巴治疗的敏感性。用（-）-司来吉兰预处理可通过抑制前体毒素向毒素的转化、或抑制神经元再摄取机制、或这两个过程的组合来预防神经毒素如1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）、6-羟基多巴胺、N,N-二甲基-对-苯二胺（DSP-4）、AF64A的作用。然而，不能排除该抑制剂的其他作用。（-）-司来吉兰，而非其（+）-对映体，被证明在不诱导MAO-B抑制的浓度下是嗜铬细胞瘤（PC12）细胞和人黑色素瘤细胞程序性细胞死亡（凋亡）的有效抑制剂。MAO-B的活性随年龄增长而增加，与年龄相关的变化导致神经毒性剂的过度产生。抑制该酶的活性可对神经退行性脑部疾病起到预防作用。治疗中最广泛使用的MAO-B抑制剂是（-）-司来吉兰，且它没有“酪胺反应”。对于缺乏前一种效应的复杂机制尚不完全清楚。
