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	C₁₇H₁₇CLN₂O
Molecular Weight	300.78
Exact Mass	300.102
CAS #	21715-46-8
Related CAS #	Etifoxine hydrochloride;56776-32-0;Etifoxine-d5;1346598-10-4
PubChem CID	135413553
Appearance	Light yellow to yellow solid powder
Density	1.2±0.1 g/cm3
Boiling Point	421.2±55.0 °C at 760 mmHg
Melting Point	90-92
Flash Point	208.5±31.5 °C
Vapour Pressure	0.0±1.0 mmHg at 25°C
Index of Refraction	1.601
LogP	3.78
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	2
Heavy Atom Count	21
Complexity	394
Defined Atom Stereocenter Count	0
InChi Key	IBYCYJFUEJQSMK-UHFFFAOYSA-N
InChi Code	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)
Chemical Name	6-chloro-N-ethyl-4-methyl-4-phenyl-1H-3,1-benzoxazin-2-imine
Synonyms	HOE 36-801HOE 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
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 doses, etifoxine competitively reduces [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: intraperitoneal (ip) injection. 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.
Additional Infomation	Etifoxine is a benzoxazine. Etifoxine is an anxiolytic and anticonvulsant drug developed by Hoechst in the 1960s. It is used in anxiety disorders and to promote peripheral nerve healing. It does not bind to the benzodiazepine receptor though the effects are similar to that of benzodiazepines. It is more effective than lorazepam as an anxiolytic, and has fewer side effects. Etifoxine has been associated with acute liver injury.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~332.47 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.31 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 (8.31 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 (8.31 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	3.3247 mL	16.6234 mL	33.2469 mL
	5 mM	0.6649 mL	3.3247 mL	6.6494 mL
	10 mM	0.3325 mL	1.6623 mL	3.3247 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.