title: Interactions of etifoxine with the chloride channel coupled to the GABA(A) receptor complex.
abstract: This study examined the nature of the interactions of etifoxine, an anxiolytic and anticonvulsant compound, with the GABA(A) 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 GABA(A) 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 GABA(A) receptors, had no effect on the action of etifoxine. These findings suggest that etifoxine exerts its effect by interacting with the Cl- channel of GABA(A) receptors and probably by facilitating GABAergic inhibition.
authors.affiliation: Département de Pharmacologie, Zac de Mercières, Chemin d'Armancourt, Strasbourg, France.
authors.forename: M
authors.initials: M
authors.lastname: Verleye
authors.forename: R
authors.initials: R
authors.lastname: Schlichter
authors.forename: J M
authors.initials: JM
authors.lastname: Gillardin
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects* / Q000502:physiology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000502:physiology; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology; D003292:Convulsants / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D010078:Oxazines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000927:Anticonvulsants; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018118:Chloride Channels; D003292:Convulsants; D018757:GABA Modulators; D010078:Oxazines; D011963:Receptors, GABA-A; D005442:Flumazenil; C037476:tert-butylbicyclophosphorothionate; C002125:etifoxine