6,7-Dichloroquinoxaline-2,3-dione is a competitive antagonist specific to strychnine-insensitive [3H]glycine binding sites on the N-methyl-D-aspartate receptor complex.
Multiple binding sites on the N-methyl-D-aspartate (NMDA) receptor complex were examined using rat brain synaptic membranes treated with Triton X-100. Binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne ([3H]MK-801), a noncompetitive NMDA antagonist, in the presence of 10 microM L-glutamate not only was inhibited by different types of antagonists, such as 6,7-dichloro-3-hydroxy-2-quinoxaline-carboxylate, 7-chlorokynurenate, and 6,7-dichloroquinoxaline-2,3-dione (DCQX), but also was abolished by non-NMDA antagonists, including 6-cyano-7-nitroquinoxaline-2,3-dione and 6,7-dinitroquinoxaline-2,3-dione. The inhibition of [3H]MK-801 binding by these compounds was invariably reversed or attenuated by addition of 10 microM glycine. Among these novel antagonists with an inhibitory potency on [3H]MK-801 binding, only DCQX abolished [3H]glycine binding without inhibiting [3H]glutamate and [3H](+-)-3-(2-carboxypiperazine-4-yl)propyl-1-phosphonate bindings. Other antagonists examined were all effective as displacers of the latter two bindings. These results suggest that DCQX is an antagonist highly selective to the strychnine-insensitive glycine binding sites with a relatively high affinity.
Ogita
K
K
Department of Pharmacology, Setsunan University, Osaka, Japan.
Yoneda
Y
Y
D000818:Animals; D001665:Binding Sites; D003986:Dibenzocycloheptenes / Q000378:metabolism; D016291:Dizocilpine Maleate; D004351:Drug Resistance; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005998:Glycine / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013331:Strychnine / Q000494:pharmacology*; D013570:Synaptic Membranes / Q000378:metabolism; D014316:Tritium
D003986:Dibenzocycloheptenes; D005971:Glutamates; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D014316:Tritium; D018698:Glutamic Acid; C061603:6,7-dichloroquinoxaline-2,3-dione; D016291:Dizocilpine Maleate; D013331:Strychnine; D005998:Glycine