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

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 α₁β₂γ_2S, α₁β₃γ_2S, α₂β₂γ_2S and α₂β₃γ_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.