Etifoxine

drugbox
IUPAC_name = 6-chloro-"N"-ethyl-4-methyl-4-phenyl- 4"H"-benzo ["d"] [1,3] oxazin-2-amine

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CAS_number = 21715-46-8
ATC_prefix = N05
ATC_suffix = BX03
PubChem = 30768
DrugBank =
C=17|H=17|Cl=1|N=2|O=1
molecular_weight = 300.782 g/mol
bioavailability = 90%
protein_bound =
metabolism = Hepatic (no CYP450 interactions)
elimination_half-life = 2 to 6 hours (etifoxine), 20 to 30 hours (active metabolite) [cite web |url=http://www.adcock.co.za/Resources/ProductDocs/Stresam%20PI.pdf |title=Stresam PI |date=n.d. |publisher=Adcock Ingram |accessdate=2008-08-30]
excretion = Renal
pregnancy_category= Not recommended. Crosses the placental barrier
legal_AU =
legal_CA =
legal_UK =
legal_US =
legal_status =
routes_of_administration = Oral

Etifoxine (INN, also known as etafenoxine; trade name Stresam) is an anxiolytic and anticonvulsant drug. [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.] It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. [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.] It is more effective than lorazepam as an anxiolytic, but has less side effects. [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.]

Etifoxine has been associated with acute liver injury.cite journal |author=Mennecier D, Rimlinger H, Gidenne S, "et al" |title= [Etifoxine chlorhydrate-induced acute hepatitis] |language=French |journal=Gastroenterol. Clin. Biol. |volume=27 |issue=11 |pages=1050–1 |year=2003 |month=November |pmid=14732859 |doi= |url=http://www.em-consulte.com/article/129761]

Mechanism of action

Unlike benzodiazepines, etifoxine appears to produce its anxiolytic effects by binding to β2 and β3 subunits of the GABA_A 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. [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.] This difference in binding means that etifoxine can be used alongside benzodiazepines to potentiate their effects without competing for binding sites, [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.] however it also means that the effects of etifoxine are not reversed by the benzodiazepine antagonist flumazenil. [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.]

References

* The Merck Index, 12th Edition. 3910