Ohno K, Okada M, Tsutsumi R, Sakamoto S, Yamaguchi T
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Miyukigaoka, Tsukuba, Japan.
Jpn J Pharmacol. 1998 Jan;76(1):105-8. doi: 10.1254/jjp.76.105.
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. YM90K had neuroprotective actions against both kainate toxicity and cyclothiazide-enhanced AMPA toxicity. YM90K induced a parallel and rightward shift of both kainate and AMPA dose-response curves. The application of YM90K even 3 hr after the start of kainate exposure significantly reduced kainate toxicity. These results indicate that YM90K protects neurons against AMPA receptor-mediated toxicity at an agonist site on the AMPA receptor and that YM90K protects against AMPA receptor-mediated toxicity even if applied after neurotoxic insult.
使用海藻酸、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和环噻嗪在大鼠海马体培养物中研究了YM90K对AMPA受体介导的兴奋性毒性的影响。YM90K对海藻酸毒性和环噻嗪增强的AMPA毒性均具有神经保护作用。YM90K使海藻酸和AMPA剂量反应曲线平行且向右移动。即使在海藻酸暴露开始3小时后应用YM90K，也能显著降低海藻酸毒性。这些结果表明，YM90K在AMPA受体的激动剂位点保护神经元免受AMPA受体介导的毒性，并且即使在神经毒性损伤后应用YM90K也能防止AMPA受体介导的毒性。
