M. Verleye et al., Functional modulation of gamma-aminobutyric acid(A) receptors by etifoxineand allopregnanolone in rodents, NEUROSCI L, 301(3), 2001, pp. 191-194
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.