Etifoxine ball-and-stick.png
Clinical data
Trade namesStresam
AHFS/Drugs.comInternational Drug Names
  • Not recommended. Crosses the placental barrier
Routes of
ATC code
Legal status
Legal status
  • US: Unscheduled and not FDA approved
Pharmacokinetic data
MetabolismHepatic (no CYP450 interactions)
Elimination half-life2 to 6 hours (etifoxine),[1]
CAS Number
PubChem CID
Chemical and physical data
Molar mass300.79 g·mol−1
3D model (JSmol)
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Etifoxine (INN; also known as etafenoxine; trade name Stresam) is an anxiolytic and anticonvulsant drug[2][3] developed by Hoechst in the 1960s.[4] It is sold in approximately 40 countries for anxiety disorders, without the sedation and ataxia associated with benzodiazepine drugs.[5] It has similar anxiolytic effects to benzodiazepine drugs, but is structurally distinct.[6] It is as effective as lorazepam as an anxiolytic, but has fewer side effects.[7] Etifoxine is not approved by the U.S. Food and Drug Administration or the European Medicines Agency.

Side effects[edit]

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.[8] 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.[9]

Mechanism of action[edit]

Unlike benzodiazepines, etifoxine produces its anxiolytic effects through a dual mechanism, by directly binding to GABAA receptors and to the mitochondrial translocator protein (TSPO), resulting in the potentiation of the GABAergic function.

At GABAA receptors etifoxine binds at the α+β− interface and preferentially potentiates α2β3γ2 and α3β3γ2 receptor types.[10] Direct partial agonism shows through at high concentrations and is perhaps not physiologically relevant (starting at > 1 micromolar).[11] This is different than benzodiazepines and etifoxine can be used alongside benzodiazepines to potentiate their effects without competing for binding sites;[12] however, it also means that the direct effects of etifoxine are not reversed by the benzodiazepine antagonist flumazenil.[13]

Etifoxine stimulates the biosynthesis of endogenous neurosteroids, namely 17-hydroxypregnenolone, dehydroepiandrosterone, progesterone, and tetrahydroprogesterone.[14] These neurosteroids ín turn interact with the GABAA receptor.


  1. ^ "Stresam PI" (PDF). Adcock Ingram. n.d. Retrieved 2008-08-30.[dead link]
  2. ^ Kruse HJ, Kuch H (1985). "Etifoxine: evaluation of its anticonvulsant profile in mice in comparison with sodium valproate, phenytoin and clobazam". Arzneimittelforschung. 35 (1): 133–135.
  3. ^ The Merck Index, 12th Edition. 3910.
  4. ^ U.S. Patent 3,725,404
  5. ^ Girard C, Liu S, Cadepond F, Adams D, Lacroix C, Verleye M, Gillardin JM, Baulieu EE, Schumacher M, Schweizer-Groyer G (2008). "Etifoxine improves peripheral nerve regeneration and functional recovery". Proc Natl Acad Sci U S A. 105 (51): 20505–10. Bibcode:2008PNAS..10520505G. doi:10.1073/pnas.0811201106. PMC 2629330. PMID 19075249.
  6. ^ Schlichter R, Rybalchenko V, Poisbeau P, Verleye M, Gillardin J (2000). "Modulation of GABAergic synaptic transmission by the non-benzodiazepine anxiolytic etifoxine". Neuropharmacology. 39 (9): 1523–35. doi:10.1016/s0028-3908(99)00253-1. PMID 10854897.
  7. ^ Nguyen N, Fakra E, Pradel V, Jouve E, Alquier C, Le Guern ME, Micallef J, Blin O (2006). "Efficacy of etifoxine compared to lorazepam monotherapy in the treatment of patients with adjustment disorders with anxiety: a double-blind controlled study in general practice". Human Psychopharmacology. 21 (3): 139–49. doi:10.1002/hup.757. PMID 16625522.
  8. ^ Choi, Y. M.; Kim, K. H. (2015). "Etifoxine for Pain Patients with Anxiety". The Korean Journal of Pain. 28 (1): 4–10. doi:10.3344/kjp.2015.28.1.4. PMC 4293506. PMID 25589941.
  9. ^ "COMMISSION NATIONALE DE PHARMACOVIGILANCE Compte rendu de la réunion du mardi 26 juin 2012" (PDF).
  10. ^ Mattei C, Taly A, Soualah Z, Saulais O, Henrion D, Guérineau NC, Verleye M, Legros C (2019). "Involvement of the GABAA receptor α subunit in the mode of action of etifoxine". Pharmacol. Res. doi:10.1016/j.phrs.2019.04.034. PMID 31059790.
  11. ^ Hamon A, Morel A, Hue B, Verleye M, Gillardin JM (2003). "The modulatory effects of etifoxine's direct effects on GABA(A) receptors are mediated by the beta subunit". Neuropharmacology. 45 (3): 293–303. doi:10.1016/s0028-3908(03)00187-4. PMID 12871647.
  12. ^ Kruse HJ, Kuch H (1986). "Potentiation of clobazam's anticonvulsant activity by etifoxine, a non-benzodiazepine tranquilizer, in mice. Comparison studies with sodium valproate". Arzneimittelforschung. 36 (9): 1320–2. PMID 3098254.
  13. ^ Verleye M, Schlichter R, Gillardin JM (1999). "Interactions of etifoxine with the chloride channel coupled to the GABA(A) receptor complex". NeuroReport. 10 (15): 3207–10. doi:10.1097/00001756-199910190-00015. PMID 10574561.
  14. ^ do Rego, Jean Luc; Vaudry, David; Vaudry, Hubert (2015). "The Non-Benzodiazepine Anxiolytic Drug Etifoxine Causes a Rapid, Receptor-Independent Stimulation of Neurosteroid Biosynthesis". PLoS ONE. 10 (3): e0120473. Bibcode:2015PLoSO..1020473D. doi:10.1371/journal.pone.0120473. PMC 4364751. PMID 25785994.