Shimazu S, Katsuki H, Akaike A
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Eur J Pharmacol. 1999 Jul 14;377(1):29-34. doi: 10.1016/s0014-2999(99)00414-8.
The potential neuroprotective effect of (-)-deprenyl (R-N,alpha-dimethyl-N-2-propynylbenzeneethanamine) against N-methyl-D-aspartate (NMDA) excitotoxicity was investigated on rat mesencephalic dopaminergic neurons in organotypic slice cultures. While 24 h application of NMDA (100 microM) caused a marked decrease in the number of surviving dopaminergic neurons, simultaneous application of (-)-deprenyl significantly attenuated the cytotoxic effect of NMDA. (+)-Deprenyl showed a less potent but still significant protective effect against NMDA insult. Pre-treatment of cultures with (-)-deprenyl conferred no protection against subsequent NMDA insult, suggesting that the protective effect of (-)-deprenyl may be independent of its irreversible inhibitory action on monoamine oxidase B. (-)-Deprenyl was also ineffective in preventing cell death induced by H2O2. These results indicated that (-)-deprenyl protects dopaminergic neurons from NMDA excitotoxicity through a mechanism distinct from monoamine oxidase inhibition or detoxification of reaction oxygen species.
在器官型脑片培养中，研究了（-）-司来吉兰（R-N，α-二甲基-N-2-丙炔基苯乙胺）对大鼠中脑多巴胺能神经元抗N-甲基-D-天冬氨酸（NMDA）兴奋性毒性的潜在神经保护作用。虽然应用NMDA（100微摩尔）24小时导致存活的多巴胺能神经元数量显著减少，但同时应用（-）-司来吉兰可显著减轻NMDA的细胞毒性作用。（+）-司来吉兰对NMDA损伤显示出较弱但仍显著的保护作用。用（-）-司来吉兰预处理培养物对随后的NMDA损伤没有保护作用，这表明（-）-司来吉兰的保护作用可能与其对单胺氧化酶B的不可逆抑制作用无关。（-）-司来吉兰在预防过氧化氢诱导的细胞死亡方面也无效。这些结果表明，（-）-司来吉兰通过一种不同于单胺氧化酶抑制或活性氧解毒的机制保护多巴胺能神经元免受NMDA兴奋性毒性的影响。
