Etifoxine (HOE 36801) and etafenoxine, is a non-benzodiazepine GABAergic anxiolytic and anticonvulsant drug developed by Hoechst in the 1960s, and sold in approximately 40 countries for anxiety disorders, without the sedation and ataxia associated with benzodiazepine drugs. 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.

Physicochemical Properties

Molecular Formula	C17H18CL2N2O
Molecular Weight	337.24362
Exact Mass	336.079
CAS #	56776-32-0
Related CAS #	Etifoxine;21715-46-8
PubChem CID	135413552
Appearance	White to off-white solid powder
Density	1.2g/cm3
Boiling Point	421.2ºC at 760mmHg
Flash Point	208.5ºC
LogP	4.859
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	2
Heavy Atom Count	22
Complexity	394
Defined Atom Stereocenter Count	0
InChi Key	SCBJXEBIMVRTJE-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H17ClN2O.ClH/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)1H
Chemical Name	6-chloro-N-ethyl-4-methyl-4-phenyl-4H-benzo[d][1,3]oxazin-2-amine hydrochloride
Synonyms	HOE 36801 HOE-36801 HOE36801 etafenoxine Stresam
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Etefosine (EFX) increases [3H]muscimol binding at equilibrium in a dose-dependent manner at concentrations between 10 and 300 μM (higher concentrations limit its solubility); at 300 μM, EFX 21 reaches 155± of its control value.
ln Vivo	At micromolar concentrations, etifoxine competitively inhibits [35S]TBPS binding in rat brain [1]. When compared to C57BL/6J mice, BALB/cByJ mice show more pronounced anxiolytic and anticonvulsant effects when exposed to etifoxine (3.125-50 mg/kg) [3].
Animal Protocol	Animal/Disease Models: Sixweeks old BALB/cByJ and C57BL/6J mice (20-25 g) [3]. Doses: 3.125-50 mg/kg. Route of Administration: intraperitonealinfection. Experimental Results: The 12.5 mg/kg dose of BALB/cByJ mice Dramatically increased arm open time compared to vehicle (p = 0.009), but had no effect in C57B/6J mice. BALB/cByJ mice demonstrated Dramatically (p < 0.012) lower plasma compound levels at 15 and 30 min compared with C57BL/6J mice.
References	[1]. Effects of etifoxine on ligand binding to GABA(A) receptors in rodents. Neurosci Res. 2002 Oct;44(2):167-72. [2]. The modulatory effects of the anxiolytic etifoxine on GABA(A) receptors are mediated by the beta subunit. Neuropharmacology. 2003 Sep;45(3):293-303. [3]. 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. 2011 Jun;21(6):457-70.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~148.26 mM) H2O : ~5 mg/mL (~14.83 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.41 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (7.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.9652 mL	14.8262 mL	29.6525 mL
	5 mM	0.5930 mL	2.9652 mL	5.9305 mL
	10 mM	0.2965 mL	1.4826 mL	2.9652 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.