Functional modulation of gamma-aminobutyric acid(A) receptors by etifoxineand allopregnanolone in rodents

We looked for an interaction between etifoxine and the neurosteroid allopre gnanolone at central gamma-aminobutyric acid (GABA(A)) receptors. Etifoxine (2 muM) did not affect the affinity of allopregnanolone (IC50 = 108 nM) fo r its site in preparations of Sprague-Dawley rat cerebral cortex membranes, as determined by the inhibition of [S-35] t-butylbicyclo-phosphorothionate binding, a specific ligand of the GABA(A) receptor chloride channel site. Etifoxine and allopregnanolone were anticonvulsants, blocking the clonic co nvulsions induced by bicuculline tan antagonist of the GABA(A) receptor) in CD1 mice. A combination of subactive doses of the two compounds showed add itive anticonvulsant effects. These results suggest that etifoxine and allo pregnanolone bind to distinct putative recognition sites at or near the chl oride channel site. Functionally, their binding may have an additive effect by enhancing GABA(A) inhibitory transmission. (C) 2001 Elsevier Science Ir eland Ltd. All rights reserved.