COMPARISON OF NEUROPROTECTIVE EFFICACY OF COMPETITIVE AND NONCOMPETITIVE AMPA ANTAGONISTS IN-VITRO

The neuroprotective efficacy of the most potent competitive lpha-amino -3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist -dihyd roxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) and three recently developed 2,3-benzodiazepine non-competitive AMPA antagonists (GYKI 5 2466, 53405 and 53655) was investigated in primary cultures of rat tel encephalic neurons. NBQX protected cultured neurons against AMPA (20 m u M for 21-23 h) induced toxicity with EC(50) of 0.5 mu M. In the same test GYKI 52466, 53405 and 53655 had EC(50) values of 10.6, 9.3 and 5 .1 mu M, respectively. Thus we found the competitive antagonist NBQX t o be ten times more effective neuroprotectant in vitro than the most p otent non-competitive GYKI compound (GYKI 53655). (C) 1997 Elsevier Sc ience B.V.