Lustig H S, von Brauchitsch K L, Chan J, Greenberg D A
Department of Neurology, University of California, San Francisco 94110.
Neurosci Lett. 1992 Aug 31;143(1-2):229-32. doi: 10.1016/0304-3940(92)90271-8.
Excessive release of glutamate has been implicated in the pathogenesis of excitotoxic neurologic disorders, such as stroke. BW 1003C87, an inhibitor of glutamate release and a putative Na+ channel antagonist, reduced veratridine-stimulated, tetrodotoxin- and dizocilpine-sensitive toxicity (measured by lactate dehydrogenase efflux) in neuron-enriched cortical cultures (IC50 = 5 microM). In contrast, BW 1003C87 (300 microM) had no effect on toxicity induced by direct application of 1 mM glutamate or 1 mM N-methyl-D-aspartate, or by depolarization with 50 mM KCl. Glutamate release inhibitors such as BW 1003C87 may provide a novel approach to protection from excitotoxicity.
谷氨酸的过度释放与兴奋性毒性神经疾病（如中风）的发病机制有关。BW 1003C87是一种谷氨酸释放抑制剂和一种假定的钠通道拮抗剂，可降低富含神经元的皮质培养物中藜芦碱刺激的、对河豚毒素和地卓西平敏感的毒性（通过乳酸脱氢酶外排测量）（IC50 = 5 microM）。相比之下，BW 1003C87（300 microM）对直接应用1 mM谷氨酸或1 mM N-甲基-D-天冬氨酸或用50 mM KCl去极化诱导的毒性没有影响。像BW 1003C87这样的谷氨酸释放抑制剂可能为预防兴奋性毒性提供一种新方法。
