Felbamate inhibits [H-3]t-butylbicycloorthobenzoate (TBOB) binding and enhances Cl- current at the gamma-aminobutyric acid(A) (GABA(A)) receptor

We investigated the interaction of felbamate (FBM) with gamma-aminobutyric acid type A receptors using receptor autoradiography with [H-3]t-butylbicycloorthobenzoate (TBOB) and whole-cell patch-clamp recordings of cultured mouse cortical neurons. FBM produced dose-dependent inhibition of [H-3]TBOB binding with IC50 values of approximately 250 mu M. Saturation analysis in the presence of FBM revealed increased K-d and decreased B-max. Dissociation initiated by picrotoxin (PTX) was accelerated by FBM. The regional pattern of [H-3]TBOB binding inhibition by FBM was different from the regional modulation of [H-3]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 mu M but not 3 mu M or 100 mu M. 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 hat interacts with the PTX site but is distinct from the PTX barbiturate, GABA, benzodiazepine, zinc and neurosteroid sites.