Effects of etifoxine on ligand binding to GABA(A) receptors in rodents.
Neurosci Res
; 44(2): 167-72, 2002 Oct.
Article
en En
| MEDLINE
| ID: mdl-12354631
The GABA(A) receptor/chloride ionophore is allosterically modulated by several classes of anxiolytic and anticonvulsant agents, including benzodiazepines, barbiturates and neurosteroids. Etifoxine, an anxiolytic and anticonvulsant compound competitively inhibited the binding of [(35)S]t-butylbicyclophosphoro-thionate (TBPS), a specific ligand of the GABA(A) receptor chloride channel site. To investigate the etifoxine modulatory effects on the different binding sites of the GABA(A) receptor complex, we have examined the effects of etifoxine on binding of the receptor agonist [(3)H]muscimol and the benzodiazepine modulator [(3)H]flunitrazepam in rat brain membrane preparations. The anticonvulsant properties of etifoxine combined with muscimol and flunitrazepam were performed in mice with picrotoxin-induced clonic seizures. Etifoxine modestly enhanced binding of [(3)H]muscimol and of [(3)H]flunitrazepam by increasing the number of binding sites without changing the binding affinity of [(3)H]flunitrazepam. In contrast, the compound decreased the affinity of muscimol for its binding site. In vivo, the combination of subactive doses of etifoxine with muscimol or flunitrazepam produced an anticonvulsant additive effect against the picrotoxin-induced clonic seizures in mice. These results suggest that the interaction of etifoxine on the GABA(A) receptor complex would allosterically modify different binding sites due to conformational changes. Functionally, the resulting facilitation of GABA transmission underlies the pharmacological properties of etifoxine.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oxazinas
/
Encéfalo
/
Membrana Celular
/
Receptores de GABA-A
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
Neurosci Res
Asunto de la revista:
NEUROLOGIA
Año:
2002
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Irlanda