A potent antagonist of the strychnine insensitive glycine receptor has anticonvulsant properties.
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.
Sheardown
M J
MJ
A/S Ferrosan, CNS Division, Sydmarken, Soeborg, Denmark.
Drejer
J
J
Jensen
L H
LH
Stidsen
C E
CE
Honoré
T
T
D000818:Animals; D000927:Anticonvulsants; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D013181:Cortical Spreading Depression / Q000187:drug effects; D005260:Female; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016202:N-Methylaspartate; D011247:Pregnancy; D011760:Pyrrolidinones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013331:Strychnine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D011760:Pyrrolidinones; D011810:Quinoxalines; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; C063295:5,7-dinitroquinoxaline-2,3-dione; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; C001369:1-hydroxy-3-amino-2-pyrrolidone; D013331:Strychnine; D005998:Glycine