WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H526737
CAS#: 56776-32-0 (HCl)
Description: Etifoxine, also known as HOE 36801 and etafenoxine, is an anxiolytic and anticonvulsant drug developed by Hoechst in the 1960s. 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.
Hodoodo Cat#: H526737
Name: Etifoxine HCl
CAS#: 56776-32-0 (HCl)
Chemical Formula: C17H18Cl2N2O
Exact Mass: 300.10
Molecular Weight: 337.244
Elemental Analysis: C, 60.55; H, 5.38; Cl, 21.02; N, 8.31; O, 4.74
Related CAS #: 21715-46-8 (free) 56776-32-0 (HCl)
Synonym: HOE 36801; HOE-36801; HOE36801; Etifoxine; etafenoxine. trade name Stresam
IUPAC/Chemical Name: 6-chloro-N-ethyl-4-methyl-4-phenyl-4H-benzo[d][1,3]oxazin-2-amine hydrochloride
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
SMILES Code: CC1(C2=CC=CC=C2)C3=CC(Cl)=CC=C3N=C(NCC)O1.[H]Cl
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: It is used in some countries for anxiety disorders. It has similar effects to benzodiazepine drugs, but is structurally distinct and does not bind to the benzodiazepine receptor. It is more effective than lorazepam as an anxiolytic, and has fewer side effects. Etifoxine is not approved by the U.S. Food and Drug Administration or the European Medicines Agency.
| Biological target: | Etifoxine hydrochloride is a positive allosteric modulator of α1β2γ2 and α1β3γ2 subunit-containing GABAA receptors. |
| In vitro activity: | In neuronal cultures intoxicated with Aβ1-42, etifoxine dose-dependently decreased oxidative stress (methionine sulfoxide positive neurons), tau-hyperphosphorylation and synaptic loss (ratio PSD95/synaptophysin). Reference: CNS Neurol Disord Drug Targets. 2020;19(3):227-240. https://pubmed.ncbi.nlm.nih.gov/32479250/ |
| In vivo activity: | The intraperitoneal EFX (etifoxine) treatment for five consecutive days (50 mg/kg) relieved mechanical allodynia in a sustained manner. Besides its effect on evoked mechanical hypersensitivity, EFX also alleviated aversiveness of ongoing pain as well as anxiodepressive-like consequences of neuropathic pain following cuff-induced mononeuropathy. This study suggests that EFX presents promising therapeutic potential for the relief of both somatosensory and affective consequences of neuropathic pain, a beneficial effect that is likely to involve monoamine descending controls. Reference: Neuropharmacology. 2021 Jan;182:108407. https://pubmed.ncbi.nlm.nih.gov/33212115/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 41.9 | 124.12 | |
| Water | 1.7 | 5.01 |
The following data is based on the product molecular weight 337.24 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Riban V, Meunier J, Buttigieg D, Villard V, Verleye M. In Vitro and In Vivo Neuroprotective Effects of Etifoxine in β-Amyloidinduced Toxicity Models. CNS Neurol Disord Drug Targets. 2020;19(3):227-240. doi: 10.2174/1871527319666200601151007. PMID: 32479250. 2. Kokova VY, Zagorchev PI, Apostolova EG, Peychev LP. Etifoxine does not impair muscle tone and motor function in rats as assessed by in vivo and in vitro methods. Gen Physiol Biophys. 2020 Mar;39(2):179-186. doi: 10.4149/gpb_2019053. PMID: 32329445. 3. Kamoun N, Gazzo G, Goumon Y, Andry V, Yalcin I, Poisbeau P. Long-lasting analgesic and neuroprotective action of the non-benzodiazepine anxiolytic etifoxine in a mouse model of neuropathic pain. Neuropharmacology. 2021 Jan;182:108407. doi: 10.1016/j.neuropharm.2020.108407. Epub 2020 Nov 16. PMID: 33212115. 4. Zhang H, Ma L, Guo WZ, Jiao LB, Zhao HY, Ma YQ, Hao XM. TSPO ligand etifoxine attenuates LPS-induced cognitive dysfunction in mice. Brain Res Bull. 2020 Dec;165:178-184. doi: 10.1016/j.brainresbull.2020.10.013. Epub 2020 Oct 16. PMID: 33075418. |
| In vitro protocol: | 1. Riban V, Meunier J, Buttigieg D, Villard V, Verleye M. In Vitro and In Vivo Neuroprotective Effects of Etifoxine in β-Amyloidinduced Toxicity Models. CNS Neurol Disord Drug Targets. 2020;19(3):227-240. doi: 10.2174/1871527319666200601151007. PMID: 32479250. 2. Kokova VY, Zagorchev PI, Apostolova EG, Peychev LP. Etifoxine does not impair muscle tone and motor function in rats as assessed by in vivo and in vitro methods. Gen Physiol Biophys. 2020 Mar;39(2):179-186. doi: 10.4149/gpb_2019053. PMID: 32329445. |
| In vivo protocol: | 1. Kamoun N, Gazzo G, Goumon Y, Andry V, Yalcin I, Poisbeau P. Long-lasting analgesic and neuroprotective action of the non-benzodiazepine anxiolytic etifoxine in a mouse model of neuropathic pain. Neuropharmacology. 2021 Jan;182:108407. doi: 10.1016/j.neuropharm.2020.108407. Epub 2020 Nov 16. PMID: 33212115. 2. Zhang H, Ma L, Guo WZ, Jiao LB, Zhao HY, Ma YQ, Hao XM. TSPO ligand etifoxine attenuates LPS-induced cognitive dysfunction in mice. Brain Res Bull. 2020 Dec;165:178-184. doi: 10.1016/j.brainresbull.2020.10.013. Epub 2020 Oct 16. PMID: 33075418. |
1: Ravikumar B, Crawford D, Dellovade T, Savinainen A, Graham D, Liere P, Oudinet JP, Webb M, Hering H. Differential efficacy of the TSPO ligands etifoxine and XBD-173 in two rodent models of Multiple Sclerosis. Neuropharmacology. 2016 Sep;108:229-37. doi: 10.1016/j.neuropharm.2016.03.053. Epub 2016 Mar 30. PubMed PMID: 27039042.
2: Zeitler A, Kamoun N, Goyon S, Wahis J, Charlet A, Poisbeau P, Darbon P. Favouring inhibitory synaptic drive mediated by GABAA receptors in the basolateral nucleus of the amygdala efficiently reduces pain symptoms in neuropathic mice. Eur J Neurosci. 2016 Apr;43(8):1082-8. doi: 10.1111/ejn.13217. Epub 2016 Mar 17. PubMed PMID: 26913957.
3: Bouillot C, Bonnefoi F, Liger F, Zimmer L. A microPET comparison of the effects of etifoxine and diazepam on [(11)C]flumazenil uptake in rat brains. Neurosci Lett. 2016 Jan 26;612:74-9. doi: 10.1016/j.neulet.2015.11.042. Epub 2015 Nov 28. PubMed PMID: 26644334.
4: Cottin J, Gouraud A, Jean-Pastor MJ, Dautriche AD, Boulay C, Geniaux H, Auffret M, Bernard N, Descotes J, Vial T. Safety profile of etifoxine: A French pharmacovigilance survey. Fundam Clin Pharmacol. 2016 Apr;30(2):147-52. doi: 10.1111/fcp.12169. Epub 2016 Jan 26. PubMed PMID: 26588183.
5: do Rego JL, Vaudry D, Vaudry H. The non-benzodiazepine anxiolytic drug etifoxine causes a rapid, receptor-independent stimulation of neurosteroid biosynthesis. PLoS One. 2015 Mar 18;10(3):e0120473. doi: 10.1371/journal.pone.0120473. eCollection 2015. PubMed PMID: 25785994; PubMed Central PMCID: PMC4364751.
6: Wolf L, Bauer A, Melchner D, Hallof-Buestrich H, Stoertebecker P, Haen E, Kreutz M, Sarubin N, Milenkovic VM, Wetzel CH, Rupprecht R, Nothdurfter C. Enhancing neurosteroid synthesis--relationship to the pharmacology of translocator protein (18 kDa) (TSPO) ligands and benzodiazepines. Pharmacopsychiatry. 2015 Mar;48(2):72-7. doi: 10.1055/s-0034-1398507. Epub 2015 Feb 5. PubMed PMID: 25654303.
7: Stein DJ. Etifoxine versus alprazolam for the treatment of adjustment disorder with anxiety: a randomized controlled trial. Adv Ther. 2015 Jan;32(1):57-68. doi: 10.1007/s12325-015-0176-6. Epub 2015 Jan 27. PubMed PMID: 25620535; PubMed Central PMCID: PMC4311065.
8: Choi YM, Kim KH. Etifoxine for pain patients with anxiety. Korean J Pain. 2015 Jan;28(1):4-10. doi: 10.3344/kjp.2015.28.1.4. Epub 2015 Jan 2. Review. PubMed PMID: 25589941; PubMed Central PMCID: PMC4293506.
9: Juif PE, Melchior M, Poisbeau P. Characterization of the fast GABAergic inhibitory action of etifoxine during spinal nociceptive processing in male rats. Neuropharmacology. 2015 Apr;91:117-22. doi: 10.1016/j.neuropharm.2014.12.022. Epub 2014 Dec 26. PubMed PMID: 25545681.
10: Djabrouhou N, Guermouche MH. Development of a stability-indicating HPLC method of etifoxine with characterization of degradation products by LC-MS/TOF, 1H and 13C NMR. J Pharm Biomed Anal. 2014 Nov;100:11-20. doi: 10.1016/j.jpba.2014.07.017. Epub 2014 Jul 27. PubMed PMID: 25117950.
11: Poisbeau P, Keller AF, Aouad M, Kamoun N, Groyer G, Schumacher M. Analgesic strategies aimed at stimulating the endogenous production of allopregnanolone. Front Cell Neurosci. 2014 Jun 17;8:174. doi: 10.3389/fncel.2014.00174. eCollection 2014. Review. PubMed PMID: 24987335; PubMed Central PMCID: PMC4060572.
12: Dai T, Zhou X, Li Y, He B, Zhu Z, Zheng C, Zhu S, Zhu Q, Liu X. Etifoxine promotes glia-derived neurite outgrowth in vitro and in vivo. J Reconstr Microsurg. 2014 Jul;30(6):381-8. doi: 10.1055/s-0034-1381751. Epub 2014 Jun 23. PubMed PMID: 24956483.
13: Zhou X, He B, Zhu Z, He X, Zheng C, Xu J, Jiang L, Gu L, Zhu J, Zhu Q, Liu X. Etifoxine provides benefits in nerve repair with acellular nerve grafts. Muscle Nerve. 2014 Aug;50(2):235-43. doi: 10.1002/mus.24131. Epub 2014 May 15. PubMed PMID: 24273088.
14: Aouad M, Zell V, Juif PE, Lacaud A, Goumon Y, Darbon P, Lelievre V, Poisbeau P. Etifoxine analgesia in experimental monoarthritis: a combined action that protects spinal inhibition and limits central inflammatory processes. Pain. 2014 Feb;155(2):403-12. doi: 10.1016/j.pain.2013.11.003. Epub 2013 Nov 14. PubMed PMID: 24239672.
15: Aouad M, Petit-Demoulière N, Goumon Y, Poisbeau P. Etifoxine stimulates allopregnanolone synthesis in the spinal cord to produce analgesia in experimental mononeuropathy. Eur J Pain. 2014 Feb;18(2):258-68. doi: 10.1002/j.1532-2149.2013.00367.x. Epub 2013 Jul 24. PubMed PMID: 23881562.
16: Daugherty DJ, Selvaraj V, Chechneva OV, Liu XB, Pleasure DE, Deng W. A TSPO ligand is protective in a mouse model of multiple sclerosis. EMBO Mol Med. 2013 Jun;5(6):891-903. doi: 10.1002/emmm.201202124. Epub 2013 May 17. PubMed PMID: 23681668; PubMed Central PMCID: PMC3779450.
17: Zhou X, He X, He B, Zhu Z, Zheng C, Xu J, Jiang L, Gu L, Zhu J, Zhu Q, Liu X. Etifoxine promotes glial derived neurotrophic factor induced neurite outgrowth in PC12 cells. Mol Med Rep. 2013 Jul;8(1):75-80. doi: 10.3892/mmr.2013.1474. Epub 2013 May 13. PubMed PMID: 23670018.
18: Etifoxine: too many serious adverse effects. Prescrire Int. 2013 Mar;22(136):73. PubMed PMID: 23593696.
19: Moch C, Rocher F, Lainé P, Lacotte J, Biour M, Gouraud A, Bernard N, Descotes J, Vial T. Etifoxine-induced acute hepatitis: a case series. Clin Res Hepatol Gastroenterol. 2012 Oct;36(5):e85-8. doi: 10.1016/j.clinre.2012.04.002. Epub 2012 May 23. PubMed PMID: 22633197.
20: Girard C, Liu S, Adams D, Lacroix C, Sinéus M, Boucher C, Papadopoulos V, Rupprecht R, Schumacher M, Groyer G. Axonal regeneration and neuroinflammation: roles for the translocator protein 18 kDa. J Neuroendocrinol. 2012 Jan;24(1):71-81. doi: 10.1111/j.1365-2826.2011.02215.x. Review. PubMed PMID: 21951109.
