Interactions of etifoxine with the chloride channel coupled to the GABAA receptor complex

THIS study examined the nature of the interactions of etifoxine, an anxiolytic and anticonvulsant compound, with the GABAA receptor/chloride channel complex. In membrane preparations of Sprague–Dawley rat cerebral cortex, etifoxine competitively inhibited the binding of [35S]t-butylbicyclophosphoro-thionate (TBPS), a specific ligand of the GABAA receptor chloride channel site. In vivo studies demonstrated an anticonvulsant effect of etifoxine (50 and 75 mg/kg, i.p.) against the clonic convulsions induced by TBPS in CD1 mice. Flumazenil (10 and 40 mg/kg, i.p.), an antagonist of benzodiazepine sites at GABAA receptors, had no effect on the action of etifoxine. These findings suggest that etifoxine exerts its effect by interacting with the Cl− channel of GABAA receptors and probably by facilitating GABAergic inhibition.