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  • Title: GYKI 53665, a 2,3-benzodiazepine, non-competitively protects cultured neurones against AMPA toxicity.
    Author: Kovács AD, Szabó G.
    Journal: Eur J Pharmacol; 1997 Jul 16; 331(1):93-6. PubMed ID: 9274935.
    Abstract:
    The nature of the neuroprotection by the competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, 6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX), and the non-competitive AMPA receptor antagonist, 1-(4-aminophenyl)-3-methylcarbamoyl-4-methyl-3,4-dihydro-7,8-methy lenedioxy-5H-2,3-benzodiazepine (GYKI 53655), was investigated in mature telencephalic neurone cultures of the rat. NBQX protected cultured neurones against AMPA-induced delayed toxicity in a competitive manner: the AMPA concentration-response curve was shifted to the right in parallel and concentration dependently. In contrast, GYKI 53655 decreased the maximal neurotoxic effect of AMPA considerably but without affecting the EC50, for AMPA toxicity, which indicated the non-competitive mode of its action. Thus we found a clear relationship between the nature of in vitro neuroprotection and the mode of AMPA channel block.
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