|AHFS/Drugs.com||International Drug Names|
|Metabolism||Hepatic (no CYP450 interactions)|
|Elimination half-life||2 to 6 hours (etifoxine),|
|Chemical and physical data|
|Molar mass||g·mol−1 300.79|
|3D model (JSmol)|
|(what is this?)|
Etifoxine (INN; also known as etafenoxine; trade name Stresam) 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 and does not bind to the benzodiazepine receptor. It 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.
The most common adverse effect of etifoxine is mild drowsiness at initial dosing. It is not associated with any withdrawal syndromes or dependence.[medical citation needed] 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 (for a ten-year pharmacovigilance period) 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 appears to produce its anxiolytic effects in humans by activation of translocator protein (TSPO), stimulating the production of GABAA-active neurosteroids that may act in conjunction with etifoxine’s direct activation of β2 and β3 subunit containing channels of the GABAA receptor complex (a different binding site than benzodiazepines. Direct activation occurs at high concentrations and is perhaps not physiologically relevant (starting at > 1 micromolar). 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 has been shown to stimulate the biosynthesis of endogenous neurosteroids, namely 17-hydroxypregnenolone, dehydroepiandrosterone, progesterone, and tetrahydroprogesterone. Several studies have shown that the synthesis of neurosteroids is essential to the pharmacological actions of etifoxine. Inhibitors of neurosteroid biosynthesis reverse the anxiolytic and analgesic actions of etifoxine in preclinical studies.
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