Etifoxine


Etifoxine is an anxiolytic and anticonvulsant drug developed by Hoechst in the 1960s. It is sold in approximately 40 countries for anxiety disorders, without the sedation and ataxia associated with benzodiazepine drugs. It has similar anxiolytic effects to benzodiazepine drugs, but is structurally distinct, although it has structural elements in common with them. Studies suggest is as effective as lorazepam as an anxiolytic, but has fewer side effects. Etifoxine is not approved by the U.S. Food and Drug Administration or the European Medicines Agency.

Side effects

The most common adverse effect of etifoxine is mild drowsiness at initial dosing. It is not associated with any withdrawal syndromes or dependence. Etifoxine shows less adverse effects of anterograde amnesia, sedation, impaired psychomotor performance, and withdrawal syndromes than those of benzodiazepines. A 2012 review of etifoxine by the French National Pharmacovigilance Committee determined that etifoxine was safe and continued to provide a favorable alternative to benzodiazepine anxiolytics. The committee found that safety concerns were rare or very rare and that the incidence of idiosyncratic hepatic problems were very rare.

Mechanism of action

Unlike benzodiazepines, etifoxine may produce its anxiolytic effects through a dual mechanism, by directly binding to GABAA receptors and to the mitochondrial translocator protein, resulting in increases in endogenous neurosteroids.
At GABAA receptors etifoxine binds at the α+β− interface and preferentially potentiates α2β3γ2 and α3β3γ2 receptor types. This direct allosteric potentiation can only be observed at relatively high concentrations and is perhaps not physiologically relevant at normal human doses. This is different than benzodiazepines and etifoxine can be used alongside benzodiazepines to potentiate their effects without competing for binding sites; however, it also means that the direct effects of etifoxine are not reversed by the benzodiazepine antagonist flumazenil.
Etifoxine stimulates the biosynthesis of endogenous neurosteroids, for example: allopregnanolone, a nanomolar potentiator of GABA activity.