Felbamate inhibits [3H]t-butylbicycloorthobenzoate (TBOB) binding and enhances Cl- current at the gamma-aminobutyric AcidA (GABAA) receptor.

We investigated the interaction of felbamate (FBM) with gamma-aminobutyric acid type A receptors using receptor autoradiography with [3H]t-butylbicycloorthobenzoate (TBOB) and whole-cell patch-clamp recordings of cultured mouse cortical neurons. FBM produced dose-dependent inhibition of [3H]T-BOB binding with IC50 values of approximately 250 microM. Saturation analysis in the presence of FBM revealed increased Kd and decreased Bmax. Dissociation initiated by picrotoxin (PTX) was accelerated by FBM. The regional pattern of [3H]TBOB binding inhibition by FBM was different from the regional modulation of [3H]TBOB binding produced by gamma-aminobutyric acid (GABA) agonists, bicuculline, zinc or neurosteroids. With electrophysiological recordings, FBM enhanced GABA-elicited Cl- currents at GABA concentrations of 10 microM but not 3 microM or 100 microM. FBM enhancement was not blocked by the benzodiazepine antagonist flumazenil, and FBM did not affect pentobarbital potentiation of GABA-elicited currents. FBM also had no effect on PTX inhibition of GABA-elicited Cl- currents. These results suggest that FBM potentiates gamma-aminobutyric acid type A receptor function, at least in part, by acting at a site that interacts with the PTX site but is distinct from the PTX, barbiturate, GABA, benzodiazepine, zinc and neurosteroid sites.