Kazushige Ohno, Masamichi Okada (*), Rie Tsutsumi, Shuichi Sakamoto and
Tokio Yamaguchi
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