The AMPA-receptor antagonist YM90K reduces AMPA receptor-mediated excitotoxicity in rat hippocampal cultures.
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.
Ohno
K
K
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Miyukigaoka, Tsukuba, Japan.
Okada
M
M
Tsutsumi
R
R
Sakamoto
S
S
Yamaguchi
T
T
D000818:Animals; D001581:Benzothiadiazines / Q000633:toxicity; D002478:Cells, Cultured; D004232:Diuretics; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000196:embryology; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D049993:Sodium Chloride Symporter Inhibitors / Q000633:toxicity; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*
D001581:Benzothiadiazines; D004232:Diuretics; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011810:Quinoxalines; D018091:Receptors, AMPA; D049993:Sodium Chloride Symporter Inhibitors; C086162:6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C004639:cyclothiazide; D007608:Kainic Acid