Etifoxine

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Etifoxine
Etifoxine.svg
Etifoxine ball-and-stick.png
Systematic (IUPAC) name
6-chloro-N-ethyl-4-methyl-4-phenyl- 4H-benzo[d][1,3]oxazin-2-amine
Clinical data
AHFS/Drugs.com International Drug Names
Pregnancy cat.
  • Not recommended. Crosses the placental barrier
Legal status
  • US: Unscheduled
Routes Oral
Pharmacokinetic data
Bioavailability 90%
Metabolism Hepatic (no CYP450 interactions)[1]
Half-life 2 to 6 hours (etifoxine), 20 to 30 hours (active metabolite)[2]
Excretion Renal[1]
Identifiers
CAS number 21715-46-8 YesY
ATC code N05BX03
PubChem CID 30768
ChemSpider 28547 YesY
UNII X24X82MX4X YesY
KEGG D07320 YesY
ChEMBL CHEMBL2106227 N
Chemical data
Formula C17H17ClN2O 
Mol. mass 300.782 g/mol
 N (what is this?)  (verify)

Etifoxine (INN,[3] also known as etafenoxine; trade name Stresam) is an anxiolytic and anticonvulsant drug[4] developed by Hoechst in the 1960s.[3] It is used in anxiety disorders and to promote peripheral nerve healing.[5] It has similar effects to benzodiazepine drugs, but is structurally distinct and does not bind to the benzodiazepine receptor.[6] It is more effective than lorazepam as an anxiolytic, and has fewer side effects.[7]

Etifoxine has been associated with acute liver injury.[1]

Mechanism of action[edit]

Unlike benzodiazepines, etifoxine appears to produce its anxiolytic effects by binding to β2 and β3 subunits of the GABAA receptor complex, and so is acting at a different target site to benzodiazepines, although the physiological effect that is produced is similar to that of benzodiazepines.[8] This difference in binding means that etifoxine can be used alongside benzodiazepines to potentiate their effects without competing for binding sites,[9] however it also means that the effects of etifoxine are not reversed by the benzodiazepine antagonist flumazenil.[10] S-etifoxine is currently being investigated as a pain management medication. It has shown promise for chemotherapy induced pain as well as neuropathic pain, with little or no sedating side effects. [11] [12] [13]

References[edit]

  1. ^ a b c Mennecier D, Rimlinger H, Gidenne S, et al (November 2003). "[Etifoxine chlorhydrate-induced acute hepatitis]". Gastroenterol. Clin. Biol. (in French) 27 (11): 1050–1. PMID 14732859. 
  2. ^ "Stresam PI". Adcock Ingram. n.d. Retrieved 2008-08-30. [dead link]
  3. ^ a b US Patent 3725404
  4. ^ Kruse HJ, Kuch H. Etifoxine: evaluation of its anticonvulsant profile in mice in comparison with sodium valproate, phenytoin and clobazam. Arzneimittelforschung. 1985;35(1):133-5.
  5. ^ Etifoxine improves peripheral nerve regeneration and functional recovery
  6. ^ Schlichter R, Rybalchenko V, Poisbeau P, Verleye M, Gillardin J. Modulation of GABAergic synaptic transmission by the non-benzodiazepine anxiolytic etifoxine. Neuropharmacology. 2000 Jul 10;39(9):1523-35.
  7. ^ Nguyen N, Fakra E, Pradel V, Jouve E, Alquier C, Le Guern ME, Micallef J, Blin O. 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. 2006 Apr;21(3):139-49.
  8. ^ Hamon A, Morel A, Hue B, Verleye M, Gillardin JM. The modulatory effects of the anxiolytic etifoxine on GABA(A) receptors are mediated by the beta subunit. Neuropharmacology. 2003 Sep;45(3):293-303.
  9. ^ Kruse HJ, Kuch H. Potentiation of clobazam's anticonvulsant activity by etifoxine, a non-benzodiazepine tranquilizer, in mice. Comparison studies with sodium valproate. Arzneimittelforschung. 1986 Sep;36(9):1320-2.
  10. ^ Verleye M, Schlichter R, Gillardin JM. Interactions of etifoxine with the chloride channel coupled to the GABA(A) receptor complex. Neuroreport. 1999 Oct 19;10(15):3207-10
  11. ^ US Patent 8110569 - Enantiomerically pure S-etifoxine, pharmaceutical compositions thereof and methods of their use http://www.google.com/patents/US8110569
  12. ^ Etifoxine (Stresam) for chemotherapy-induced pain? http://www.pharma.uzh.ch/research/neuropharmacology/researchareas/neuropharmacology/publications/Zeilhofer_Pain_2009.pdf
  13. ^ NON-ADDITIVE, NON-SEDATING PAIN RELIEVING DRUG: http://www.ng-dg.com/news.php
  • The Merck Index, 12th Edition. 3910