Mytilineou C, Radcliffe P, Leonardi E K, Werner P, Olanow C W
Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029, USA.
J Neurochem. 1997 Jan;68(1):33-9. doi: 10.1046/j.1471-4159.1997.68010033.x.
L-Deprenyl is a relatively selective inhibitor of monoamine oxidase (MAO)-B that delays the emergence of disability and the progression of signs and symptoms of Parkinson's disease. Experimentally, deprenyl has also been shown to prevent neuronal cell death in various models through a mechanism that is independent of MAO-B inhibition. We examined the effect of deprenyl on cultured mesencephalic dopamine neurons subjected to daily changes of feeding medium, an experimental paradigm that causes neuronal death associated with activation of the NMDA subtype of glutamate receptors. Both deprenyl (0.5-50 microM) and the NMDA receptor blocker MK-801 (10 microM) protected dopamine neurons from damage caused by medium changes. The nonselective MAO inhibitor pargyline (0.5-50 microM) was not protective, indicating that protection by deprenyl was not due to MAO inhibition. Deprenyl (50 microM) also protected dopamine neurons from delayed neurotoxicity caused by exposure to NMDA. Because deprenyl had no inhibitory effect on NMDA receptor binding, it is likely that deprenyl protects from events occurring downstream from activation of glutamate receptors. As excitotoxic injury has been implicated in neurodegeneration, it is possible that deprenyl exerts its beneficial effects in Parkinson's disease by suppressing excitotoxic damage.
L-司来吉兰是一种相对选择性的单胺氧化酶（MAO）-B抑制剂，可延缓帕金森病残疾的出现以及体征和症状的进展。在实验中，司来吉兰还被证明可通过一种独立于MAO-B抑制作用的机制，在各种模型中预防神经元细胞死亡。我们研究了司来吉兰对培养的中脑多巴胺神经元的影响，这些神经元每日更换培养基，这种实验模式会导致与谷氨酸受体NMDA亚型激活相关的神经元死亡。司来吉兰（0.5 - 50微摩尔）和NMDA受体阻滞剂MK-801（10微摩尔）均可保护多巴胺神经元免受培养基更换所造成的损伤。非选择性MAO抑制剂优降宁（0.5 - 50微摩尔）没有保护作用，这表明司来吉兰的保护作用并非由于MAO抑制。司来吉兰（50微摩尔）还可保护多巴胺神经元免受因暴露于NMDA所导致的延迟性神经毒性。由于司来吉兰对NMDA受体结合没有抑制作用，司来吉兰很可能是对谷氨酸受体激活下游发生的事件起到保护作用。由于兴奋性毒性损伤与神经退行性变有关，司来吉兰有可能通过抑制兴奋性毒性损伤在帕金森病中发挥其有益作用。
