Wu R M, Chen R C, Chiueh C C
Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Ann N Y Acad Sci. 2000;899:255-61. doi: 10.1111/j.1749-6632.2000.tb06191.x.
l-Deprenyl (Selegiline), a selective and irreversible type B monoamine oxidase inhibitor, has been used as an adjunct to levodopa therapy in Parkinson's disease. Recently, it is proposed as a putative neuroprotective agent in delaying the progression of cell death based on its capability of reducing the oxidative stress derived from the MAO-B dependent metabolism of dopamine, and blocking the development of MPTP-parkinsonism. However, a variety of experimental models suggest that l-deprenyl provides neuroprotection through multiple modes of mechanism other than the inhibition of MAO-B. We have previously shown that l-deprenyl protects midbrain dopamine neurons from MPP+ toxicity by a novel antioxidant effect. In the present study we examined whether the protection against MPP+ toxicity is also shared by other reversible or irreversible MAO-B inhibitors including (+)-deprenyl, Ro16-6491 and pargyline. Our data show that non of these MAO-B inhibitors changes the dopamine loss in the striatum induced by intranigral injection of MPP+. Our result suggests that l-deprenyl may possess a unique neuroprotective action on nigral neuron against MPP+ toxicity independent of the MAO-B inhibition.
左旋司来吉兰（司来吉兰）是一种选择性、不可逆的B型单胺氧化酶抑制剂，已被用作帕金森病左旋多巴治疗的辅助药物。最近，基于其降低多巴胺单胺氧化酶B（MAO-B）依赖性代谢产生的氧化应激以及阻止1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）帕金森综合征发展的能力，它被认为是一种可能的神经保护剂，可延缓细胞死亡进程。然而，多种实验模型表明，左旋司来吉兰通过抑制MAO-B以外的多种机制提供神经保护作用。我们之前已经表明，左旋司来吉兰通过一种新的抗氧化作用保护中脑多巴胺能神经元免受1-甲基-4-苯基吡啶离子（MPP+）毒性的影响。在本研究中，我们检测了其他可逆或不可逆的MAO-B抑制剂，包括右旋司来吉兰、Ro16-6491和帕吉林，是否也具有抗MPP+毒性的保护作用。我们的数据表明，这些MAO-B抑制剂均未改变黑质内注射MPP+所诱导的纹状体多巴胺丢失。我们的结果表明，左旋司来吉兰可能对黑质神经元具有独特的抗MPP+毒性的神经保护作用，且该作用独立于MAO-B抑制作用。
