Kazushige Ohno, Masamichi Okada (*), Rie Tsutsumi, Shuichi Sakamoto and
Neuroscience Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba 305, Japan
(*) To whom correspondence should be addressed.
Abstract: The effects of YM90K on alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated excitotoxicity were investigated using kainate, AMPA and cyclothiazide in rat hippocampal cultures. YM9OK had neuroprotective actions against both kainate toxicity and cyclothiazide-enhanced AMPA toxicity. YM9OK induced a parallel and rightward shift of both kainate and AMPA dose-response curves. The application of YM9OK even 3 hr after the start of kainate exposure significantly reduced kainate toxicity. These results indicate that YM9OK protects neurons against AMPA receptor-mediated toxicity at an agonist site on the AMPA receptor and that YM9OK protects against AMPA receptor-mediated toxicity even if applied after neurotoxic insult.
Keywords: YM9OK, AMPA, Excitotoxicity