NEUROPROTECTIVE EFFECTS OF A NOVEL AMPA RECEPTOR ANTAGONIST, YM872

QUINOXALINEDIONES such as NBQX are neuroprotective in most models of c erebral ischemia but their poor solubility results in nephrotoxicity l imiting their clinical utility. We have investigated the neuroprotecti ve effects of a water soluble AMPA receptor antagonist, YM872, using t wo in vitro models. The viability of cortical cultures exposed to 400 mu M AMPA for 15 min (16.4 +/- 2.6%; n = 10) was significantly (p < 0. 05) increased (84.7 +/- 4.6%; n = 6) with YM872 (10 mu M) in a concent ration-dependent manner. Evoked post-synaptic response amplitudes in o xygen-glucose deprived hippocampal slices treated with 10 mu M YM872 ( 3.5 +/- 0.3 mV; n = 27) were significantly different from untreated de prived slices (0.3 +/- 0.1 mV; n = 31, p < 0.05) and the CA1 neurons a ppeared viable using a confocal live/dead fluorescence assay with conf ocal microscopy. The neuroprotection seen with YM872 in vitro warrants further investigation in vivo. (C) 1998 Rapid Science Ltd.