Quinoxaline derivatives are high-affinity antagonists of the NMDA receptor-associated glycine sites.
Membranes from rat telencephalon contain strychnine-insensitive glycine binding sites associated with NMDA receptors. Three quinoxaline derivatives, among them the high-affinity AMPA receptor antagonists CNQX and DNQX, were found to inhibit [3H]glycine binding to these sites with micromolar affinities. Binding of these compounds to the glycine site also inhibited glutamate-stimulated association and dissociation of [3H]TCP. This suggests that these AMPA antagonists, like the structurally related compound kynurenate, act as glycine site antagonists.
Kessler
M
M
Center for the Neurobiology of Learning and Memory, Bonney Center, University of California, Irvine 92717.
Baudry
M
M
Lynch
G
G
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D005998:Glycine / Q000378:metabolism*; D011810:Quinoxalines / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000145:classification / Q000187:drug effects / Q000378:metabolism*
D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C056723:FG 9041; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D005998:Glycine