Journal of Clinical & Experimental Pharmacology

Etifoxin, unlike benzodiazepines, potentiate GABA receptors in an α subunit-dependent manner

World Congress on Pharmacology

July 20-22, 2015 Brisbane, Australia

Cesar Mattei

Posters-Accepted Abstracts: Clin Exp Pharmacol

Abstract:

Anxiety is a common disorder that affects millions of people every year. To treat it, anxiolytic molecules enhance GABAA receptors, thus increasing central inhibition in the human brain. Benzodiazepine (BZD) molecules have been used for decades to reduce anxiety, but with sedative effects. Their pharmacological profile over GABA receptors is well characterized. The non-benzodiazepine Etifoxin (EFX) also acts with anxiolytic effects but with no undesired neurological effect. However, its precise mechanism is unknown. Here, we combined two-electrode voltage clamp experiments in Xenopus oocytes expressing different GABA receptor subtypes and behavioural experiments on mice to investigate the putative selectivity of EFX for GABA receptors as a function of their stoechiometry. Our data show that EFX exerts its positive modulation in a strictly dependent-manner, acting on α2 and α3-containing receptors and without any effect on α4-containing subtypes, and a weak effect on α5- and α6-. Contrary to BZD molecules, EFX doesn�??t rely on the third γorδ subunit to enhance GABA activation. We propose a docking model of EFX on GABA receptors, based on the recently crystallized β3 subunit. These results add to the knowledge of the GABA receptor pharmacology and suggest that EFX is an anxiolytic with anticonvulsive-like effect, with no sedative effects.