CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) antagonizes NMDA-evoked [3H]GABA release from cultured cortical neurons via an inhibitory action at the strychnine-insensitive glycine site.

The novel glutamate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) inhibited glutamate stimulated [3H]GABA release from cortical neurons in vitro. Kainate-induced release was blocked in a competitive fashion but N-methyl-D-aspartate (NMDA)-induced release was blocked non-competitively by CNQX. 7-Chlorokynurenate (7-CK) also inhibited NMDA evoked [3H]GABA release non-competitively, but had no effect on kainate induced release. The effects of both CNQX and 7-CK on NMDA-induced release were reversed by addition of exogenous glycine but the effects of CNQX on kainate-induced release were not altered by glycine. This suggests that both CNQX and 7-CK may interact with the glycine regulatory site of the NMDA receptor.