Comparison of neuroprotective efficacy of competitive and non-competitive AMPA antagonists in vitro

The neuroprotective efficacy of the most potent competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) and three recently developed 2,3-benzodiazepine non-competitive AMPA antagonists (GYKI 52466, 53405 and 53655) was investigated in primary cultures of rat telencephalic neurons. NBQX protected cultured neurons against AMPA (20 mu 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 to be ten times more effective neuroprotectant in vitro than the most potent non-competitive GYKI compound (GYKI 53655). (C) 1997 Elsevier Science B.V.