Etifoxine (
etafenoxine, Stresam®) is a non-
benzodiazepine anxiolytic with an
anticonvulsant effect. It was developed in the 1960s for
anxiety disorders and is currently being studied for its ability to promote peripheral nerve healing and to treat
chemotherapy-induced
pain. In addition to being mediated by GABAAα2 receptors like
benzodiazepines,
etifoxine appears to produce
anxiolytic effects directly by binding to β2 or β3 subunits of the GABAA receptor complex. It also modulates GABAA receptors indirectly via stimulation of
neurosteroid production after
etifoxine binds to the 18 kDa translocator
protein (TSPO) of the outer mitochondrial membrane in the central and peripheral nervous systems, previously known as the peripheral
benzodiazepine receptor (PBR). Therefore, the effects of
etifoxine are not completely reversed by the
benzodiazepine antagonist
flumazenil.
Etifoxine is used for various emotional and bodily reactions followed by anxiety. It is contraindicated in situations such as
shock, severely impaired liver or kidney function, and severe
respiratory failure. The average dosage is 150 mg per day for no more than 12 weeks. The most common adverse effect is drowsiness at the initial stage. It does not usually cause any withdrawal syndromes. In conclusion,
etifoxine shows less adverse effects of
anterograde amnesia, sedation, impaired psychomotor performance, and withdrawal syndromes than those of
benzodiazepines. It potentiates GABAA receptor-function by a direct allosteric effect and by an indirect mechanism involving the activation of TSPO. It seems promising that non-
benzodiazepine anxiolytics including
etifoxine will replenish shortcomings of
benzodiazepines and
selective serotonin reuptake inhibitors according to animated studies related to TSPO.