Tozzi A, Costa C, Di Filippo M, Tantucci M, Siliquini S, Belcastro V, Parnetti L, Picconi B, Calabresi P
Clinica Neurologica, Università degli Studi di Perugia, Ospedale S. Maria della Misericordia, Via S. Andrea delle Fratte, Perugia 06156, Italy.
Exp Neurol. 2007 Oct;207(2):218-26. doi: 10.1016/j.expneurol.2007.06.008. Epub 2007 Jun 29.
Memantine, a low-affinity uncompetitive NMDA receptor antagonist, has been widely utilized for the treatment of Alzheimer's disease. A possible neuroprotective role of this drug in pathophysiological conditions involving an altered energetic metabolism of the basal ganglia has never been addressed. Thus, we have characterized the electrophysiological effect of memantine on striatal spiny neurons recorded under control conditions and after in vitro ischemia (oxygen and glucose deprivation). Memantine reduced in a dose-dependent manner (EC(50)=5 microM) the irreversible loss of field potential amplitude induced by in vitro ischemia. The neuroprotective effect of memantine against in vitro ischemia was even more potent (EC(50)=3.2 microM) in the absence of external magnesium, a condition enhancing NMDA-mediated glutamatergic transmission. Memantine was also able to block long-term potentiation recorded from spiny neurons following a brief ischemic episode. Moreover, memantine showed protection against irreversible field potential loss induced by 3-nitropropionic acid (3-NP), an inhibitor of the mitochondrial complex II, without influencing toxicity induced by rotenone, a complex I inhibitor. Memantine could represent a potential neuroprotective agent in pathophysiological conditions involving an altered energy metabolism of basal ganglia.
美金刚是一种低亲和力的非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，已被广泛用于治疗阿尔茨海默病。该药物在涉及基底神经节能量代谢改变的病理生理状况下可能具有的神经保护作用从未得到探讨。因此，我们已对美金刚在对照条件下以及体外缺血（氧和葡萄糖剥夺）后记录的纹状体棘状神经元上的电生理效应进行了表征。美金刚以剂量依赖性方式（半数有效浓度[EC(50)] = 5微摩尔）减少了体外缺血诱导的场电位幅度的不可逆损失。在不存在外部镁离子（一种增强NMDA介导的谷氨酸能传递的条件）的情况下，美金刚对体外缺血的神经保护作用更强（EC(50) = 3.2微摩尔）。美金刚还能够阻断短暂缺血发作后从棘状神经元记录到的长时程增强。此外，美金刚对线粒体复合物II抑制剂3-硝基丙酸（3-NP）诱导的不可逆场电位损失具有保护作用，而不影响复合物I抑制剂鱼藤酮诱导的毒性。在涉及基底神经节能量代谢改变的病理生理状况下，美金刚可能代表一种潜在的神经保护剂。
