A NOVEL INHIBITOR OF GLUTAMATE RELEASE REDUCES EXCITOTOXIC INJURY INVITRO

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-mu-M). In contrast, BW 1003C87 (300 -mu-M) had no effect on toxicity induced by direct application of 1 mM glutamate or 1 mM N-methyl-D-aspartate, of by depolarization with 50 mM KCl. Glutamate release inhibitors such as BW 1003C87 may provide a novel approach to protection form excitotoxicity.