strychnine and 5-7-dinitroquinoxaline-2-3-dione

5.7-Dinitro-quinoxaline-2.3-dione (MNQX) displaced [3H]glycine binding to cortical membranes but had no effect n [3H]3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid ([3H]CPP) binding. MNQX potently antagonized N-methyl-D-aspartate (NMDA)-evoked release of [3H]GABA from cultured cortical neurones, NMDA evoked spreading depression and NMDA depolarizations in the rat neo-cortex. All of these responses were reversed by addition of glycine to the perfusion media. These results suggested that MNQX is an antagonist at the strychnine-insensitive glycine receptor associated with the NMDA receptor/ionophore complex. Furthermore the compound was found to antagonise audiogenic seizures in DBA-2 mice indicating the potential of glycine antagonists of this type in anticonvulsant therapy.

Topics: Animals; Anticonvulsants; Aspartic Acid; Cerebral Cortex; Cortical Spreading Depression; Female; gamma-Aminobutyric Acid; Glycine; In Vitro Techniques; Male; Mice; Mice, Inbred DBA; N-Methylaspartate; Pregnancy; Pyrrolidinones; Quinoxalines; Rats; Receptors, Glycine; Receptors, Neurotransmitter; Seizures; Strychnine