6-(1h-imidazol-1-yl)-7-nitro-2-3(1h-4h)-quinoxalinedione and cyclothiazide

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.

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Benzothiadiazines; Cells, Cultured; Diuretics; Drug Interactions; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Hippocampus; Kainic Acid; Neurons; Neuroprotective Agents; Quinoxalines; Rats; Rats, Wistar; Receptors, AMPA; Sodium Chloride Symporter Inhibitors