Etifoxine

Etifoxine
Clinical data
Trade namesStresam
Other namesÉtifoxine; Etifoxin; Etafenoxine; Etafenoxin; EFX; Hoe 36801; Hoe-36,801
AHFS/Drugs.comInternational Drug Names
Pregnancy
category
  • Not recommended[1]
Routes of
administration		Oral administration[2]
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability90%[3]
Protein binding88–95%[4]
MetabolismLiver[5]
MetabolitesSeveral (including diethyletifoxine)[5]
Elimination half-lifeEtifoxine: 6 hours[5]
Diethyletifoxine: 20 hours[5]
ExcretionMainly urine, also bile[5][2]
Identifiers
  • 6-Chloro-N-ethyl-4-methyl-4-phenyl-4H-benzo[d][1,3]oxazin-2-amine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.158.584 Edit this at Wikidata
Chemical and physical data
FormulaC17H17ClN2O
Molar mass300.79 g·mol−1
3D model (JSmol)
  • ClC1=CC=C2N=C(NCC)OC(C3=CC=CC=C3)(C)C2=C1
  • InChI=1S/C17H17ClN2O/c1-3-19-16-20-15-10-9-13(18)11-14(15)17(2,21-16)12-7-5-4-6-8-12/h4-11H,3H2,1-2H3,(H,19,20) checkY
  • Key:IBYCYJFUEJQSMK-UHFFFAOYSA-N checkY
  (verify)

Etifoxine, sold under the trade name Stresam among others, is a nonbenzodiazepine anxiolytic agent, primarily indicated for short-term management of adjustment disorder, specifically instances of situational depression accompanied by anxiety, such as stress-induced anxiety.[2][6] Administration is by mouth.[7] Side effects associated with etifoxine use include slight drowsiness, headache, skin eruptions, and allergic reactions.[2][8][9] In rare cases, etifoxine has been linked to severe skin and liver toxicity, as well as menstrual bleeding between periods.[8][1] Unlike benzodiazepines, etifoxine does not cause sedation or lack of coordination.[10][3] Etifoxine acts as a GABAA receptor positive allosteric modulator and as a ligand for translocator proteins.[10] Both mechanisms are conjectured to contribute to its anxiolytic properties.[10][3]

Etifoxine was developed in the 1960s and was introduced for medical use in France in 1979.[11] Its marketed in 53 countries worldwide, although it remains unavailable in the United States.[7][11][12] Throughout the 2010s and early 2020s, the safety profile of etifoxine was scrutinized within France and the European Union, prompted by reports of toxicity.[13][8][7] The investigation revealed that instances of toxicity were infrequent, and etifoxine was allowed to remain on the market.[13][8][7]

  1. ^ a b Cite error: The named reference Afect2011 was invoked but never defined (see the help page).
  2. ^ a b c d "STRESAM®, capsule Summary of Product Characteristics" (PDF). GABA Therapeutics, Inc. July 2010. Archived from the original (PDF) on 24 October 2021.
  3. ^ a b c Nuss P, Ferreri F, Bourin M (2019). "An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action". Neuropsychiatr Dis Treat. 15: 1781–1795. doi:10.2147/NDT.S200568. PMC 6615018. PMID 31308671.
  4. ^ Cite error: The named reference pmid33009629 was invoked but never defined (see the help page).
  5. ^ a b c d e Cite error: The named reference pmid25589941 was invoked but never defined (see the help page).
  6. ^ Besnier N, Blin O (January 2008). "Étifoxine : études cliniques récentes" [Etifoxine: recent clinical studies]. L'Encéphale (in French). 34 (Suppl 1 (Etifoxine : un nouveau regard sur le récepteur GABA et l'anxiété)): S9–S14. doi:10.1016/S0013-7006(08)71386-1. ISSN 0013-7006.
  7. ^ a b c d "INN/active substance: etifoxine Assessment report" (PDF). European Medicines Agency. 27 January 2022. Archived from the original (PDF) on 7 February 2023.
  8. ^ a b c d Cite error: The named reference pmid26588183 was invoked but never defined (see the help page).
  9. ^ Deplanque D, Machuron F, Waucquier N, Jozefowicz E, Duhem S, Somers S, Colin O, Duhamel A, Bordet R (August 2018). "Etifoxine impairs neither alertness nor cognitive functions of the elderly: A randomized, double-blind, placebo-controlled crossover study". Eur Neuropsychopharmacol. 28 (8): 925–932. doi:10.1016/j.euroneuro.2018.05.011. PMID 30135030. S2CID 52066957.
  10. ^ a b c Poisbeau P, Gazzo G, Calvel L (2018). "Anxiolytics targeting GABAA receptors: Insights on etifoxine". World J Biol Psychiatry. 19 (sup1): S36–S45. doi:10.1080/15622975.2018.1468030. PMID 30204559. S2CID 52191153.
  11. ^ a b Cite error: The named reference pmid31470029 was invoked but never defined (see the help page).
  12. ^ "Hermitage Man Sentenced for Importing and Selling Drugs Not Approved by FDA". www.justice.gov. 2019-10-07. Retrieved 2022-05-12.
  13. ^ a b Cite error: The named reference CNPV2012 was invoked but never defined (see the help page).