SELECTIVE BLOCKADE OF NON-NMDA RECEPTORS DOES NOT BLOCK RAPIDLY TRIGGERED GLUTAMATE-INDUCED NEURONAL DEATH

The quinoxalinedione, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), has been introduced as a relatively selective antagonist of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors. We studied the ability of CNQX to block excitatory amino acid-induced neurotoxicity in murine cortical cell cultures. 100-mu-M CNQX blocked the acute neuronal swelling induced by 500-mu-M kainate, but it also attenuated the swelling and degeneration induced by 500-mu-M NMDA. Addition of 1 mM glycine to the CNQX eliminated antagonism of NMDA toxicity, while preserving antagonism of the neuronal degeneration induced by kainate or AMPA. This selective non-NMDA antagonist combination of CNQX plus glycine substantially attenuated the acute neuronal swelling induced by brief exposure to 500-mu-M glutamate, but had little effect on subsequent late degeneration, supporting the conclusion that rapidly triggered glutamate-induced cortical neuronal death is predominantly mediated by NMDA receptors.