6,7-DICHLOROQUINOXALINE-2,3-DIONE IS A COMPETITIVE ANTAGONIST SPECIFIC TO STRYCHNINE-INSENSITIVE [H-3] 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,dcyclohepte5,10‐imine ([3H]MK‐801), a noncompetitive NMDA antagonist, in the presence of 10 μM 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 μM 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‐carboxypiperazin‐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. Copyright © 1990, Wiley Blackwell. All rights reserved