INTERACTION OF FELBAMATE WITH [H-3] DCKA-LABELED STRYCHNINE-INSENSITIVE GLYCINE RECEPTORS IN HUMAN POSTMORTEM BRAIN

The dicarbamate felbamate has been shown to be capable of competing fo r the binding of 5,7-[H-3]dichlorokynurenic acid ([H-3]DCKA) to strych nine-insensitive glycine receptors in sections of human postmortem bra in. The IC50 for this interaction was 305.8 mu M and the inhibition wa s complete at 1 mM. Autoradiographic localization of [H-3]DCKA binding revealed many regions of human brain in which strychnine-insensitive glycine receptors are manifest. The specific binding in most of these areas was markedly reduced in the presence of 625 mu M felbamate. In m any regions, [H-3]DCKA binding was reduced to background in the presen ce of felbamate, but some areas retained binding by as much as 41% (i. e., the CA2 region of the hippocampus). This is in contrast to the bin ding of [H-3]DCKA in the presence of carbamazepine, phenytoin, or valp roic acid. The binding of the glycine receptor antagonist was not affe cted by any of these latter agents to the same degree as felbamate. St rychnine-insensitive glycine receptors represent a site of action of f elbamate in the human brain. (C) 1994 Academic Press, Inc.