Felbamate is a subunit selective modulator of recombinant γ-aminobutyric acid type A receptors expressed in Xenopus oocytes

Abstract

Felbamate (2-phenyl-1,3-propanediol dicarbamate) is clinically available for the treatment of refractory epileptic seizures, and is known to modulate several ion channels including γ-aminobutyric acid type A (GABA A) receptors. To determine felbamate subunit selectivity for GABA A receptors we expressed 15 different GABA A receptor combinations in Xenopus laevis oocytes. Felbamate positively modulated GABA-currents of α 1β 2γ 2S, α 1β 3γ 2S, α 2β 2γ 2S and α 2β 3γ 2S, whereas felbamate was either ineffective or negatively modulated the other 11 receptor combinations. Regional distributions of GABA A receptor subunits suggest that felbamate may differentially modulate distinct inhibitory circuits, a possibility that may have relevance to felbamate efficacy in refractory epilepsies.