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.
Harris
K M
KM
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.
Miller
R J
RJ
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D013331:Strychnine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics*
D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D007736:Kynurenic Acid; D013331:Strychnine; C057013:7-chlorokynurenic acid; D007608:Kainic Acid; D005998:Glycine