Etifoxine

Etifoxine is a positive allosteric modulator of α₁β₂γ₂ and α₁β₃γ₂ subunit-containing GABA_A receptors.¹ It selectively increases GABA-induced currents in X. laevis oocytes expressing α₁β₂γ₂ or α₁β₃γ₂ over α₁β₁γ₂ subunit-containing receptors at 20 ?M. Etifoxine inhibits binding of the GABA_A receptor agonist muscimol in rat corticol membranes with a K_d value of 23 nM in a radioligand binding assay.² It increases NGF-induced neurite outgrowth in PC12 cells when used at a concentration of 20 ?M.³ Etifoxine (12.5 mg/kg, i.p.) increases the percentage of time spent in the open arms of the elevated plus maze in high-anxiety BALB/cByJ, but not C57BL/6, mice, indicating anxiolytic-like activity.⁴ It increases the seizure threshold in a mouse model of seizures induced by picrotoxin with a minimum effective dose (MED) of 75 mg/kg.² Etifoxine (50 mg/kg, i.p.) also increases the paw withdrawal threshold on the ipsilateral side in a rat model of rheumatoid arthritis induced by complete Freund's adjuvant.⁵

1.Hamon, A., Morel, A., Hue, B., et al.The modulatory effects of the anxiolytic etifoxine on GABAA receptors are mediated by the β subunitNeuropharmacology45(3)293-303(2003) 2.Verleye, M., Pansart, Y., and Gillardin, J.Effects of etifoxine on ligand binding to GABAA receptors in rodentsNeurosci. Res.44(2)167-172(2002) 3.Girard, C., Liu, S., Cadepond, F., et al.Etifoxine improves peripheral nerve regeneration and functional recoveryProc. Natl. Acad. Sci. USA105(51)20505-20510(2008) 4.Verleye, M., Dumas, S., Heulard, I., et al.Differential effects of etifoxine on anxiety-like behaviour and convulsions in BALB/cByJ and C57BL/6J mice: Any relation to overexpression of central GABAA receptor beta2 subunits?Eur. Neuropsychopharmacol.21(6)457-470(2011) 5.Aouad, M., Zell, V., Juif, P.E., et al.Etifoxine analgesia in experimental monoarthritis: A combined action that protects spinal inhibition and limits central inflammatory processesPain155(2)403-412(2014)