ETIFOXINE

Possibly Marketed Outside US

Details

Stereochemistry	RACEMIC
Molecular Formula	C17H17ClN2O
Molecular Weight	300.783
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCNC1=NC2=C(C=C(Cl)C=C2)C(C)(O1)C3=CC=CC=C3

InChI

InChIKey=IBYCYJFUEJQSMK-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C17H17ClN2O
Molecular Weight	300.783
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25589941
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12871647 | https://www.ncbi.nlm.nih.gov/pubmed/25545681 | https://www.ncbi.nlm.nih.gov/pubmed/24239672 | https://www.ncbi.nlm.nih.gov/pubmed/27039042

Etifoxine (etafenoxine, StresamⓇ) is a non-benzodiazepine anxiolytic with an anticonvulsant effect. It was developed in the 1960s for anxiety disorders and is currently being studied for its ability to promote peripheral nerve healing and to treat chemotherapy-induced pain. In addition to being mediated by GABA-A2 receptors like benzodiazepines, etifoxine appears to produce anxiolytic effects directly by binding to 2 or 3 subunits of the GABAA receptor complex. It also modulates GABAA receptors indirectly via stimulation of neurosteroid production after etifoxine binds to the 18 kDa translocator protein (TSPO) of the outer mitochondrial membrane in the central and peripheral nervous systems, previously known as the peripheral benzodiazepine receptor (PBR). Therefore, the effects of etifoxine are not completely reversed by the benzodiazepine antagonist flumazenil. Etifoxine is used for various emotional and bodily reactions followed by anxiety. It is contraindicated in situations such as shock, severely impaired liver or kidney function, and severe respiratory failure. The average dosage is 150 mg per day for no more than 12 weeks. The most common adverse effect is drowsiness at the initial stage. It does not usually cause any withdrawal syndromes. In conclusion, etifoxine shows less adverse effects of anterograde amnesia, sedation, impaired psychomotor performance, and withdrawal syndromes than those of benzodiazepines.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Translocator protein 12 Target ID: CHEMBL5742 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25589941	Positive Allosteric Modulator 186
GABA-A receptor; alpha-1/beta-3/gamma-2 16 Target ID: CHEMBL2094121 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25589941	Positive Allosteric Modulator 186
GABA-A receptor; alpha-1/beta-2/gamma-2 28 Target ID: CHEMBL2095172 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25589941	Positive Allosteric Modulator 186

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anxiety 275 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16625522	Primary		Approved 8583	Stresam Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
32 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/35524344/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		ETIFOXINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
68 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/35524344/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		ETIFOXINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6 h REVIEW https://pubmed.ncbi.nlm.nih.gov/25589941/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		ETIFOXINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.29% CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/35524344/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		ETIFOXINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/26588183/	unknown, ADOLESCENT\|ADULT Health Status: unknown Age Group: ADOLESCENT\|ADULT Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26588183/	Other AEs: Drowsiness, Dizziness... Other AEs: Drowsiness (36%) Dizziness (36%) Rhabdomyolysis (9%) Renal failure (9%) Sources: https://pubmed.ncbi.nlm.nih.gov/26588183/
300 mg single, oral Highest studied dose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1250945/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/1250945/	Sources: https://pubmed.ncbi.nlm.nih.gov/1250945/
150 mg 3 times / day multiple, oral Recommended Dose: 150 mg, 3 times / day Route: oral Route: multiple Dose: 150 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22633197/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22633197/	Disc. AE: Acute hepatitis... AEs leading to discontinuation/dose reduction: Acute hepatitis (grade 1-3, 100%) Sources: https://pubmed.ncbi.nlm.nih.gov/22633197/

AEs

AE	Significance	Dose	Population
Dizziness	36%	2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/26588183/	unknown, ADOLESCENT\|ADULT Health Status: unknown Age Group: ADOLESCENT\|ADULT Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26588183/
Drowsiness	36%	2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/26588183/	unknown, ADOLESCENT\|ADULT Health Status: unknown Age Group: ADOLESCENT\|ADULT Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26588183/
Renal failure	9%	2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/26588183/	unknown, ADOLESCENT\|ADULT Health Status: unknown Age Group: ADOLESCENT\|ADULT Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26588183/
Rhabdomyolysis	9%	2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/26588183/	unknown, ADOLESCENT\|ADULT Health Status: unknown Age Group: ADOLESCENT\|ADULT Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26588183/
Acute hepatitis	grade 1-3, 100% Disc. AE	150 mg 3 times / day multiple, oral Recommended Dose: 150 mg, 3 times / day Route: oral Route: multiple Dose: 150 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22633197/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22633197/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/135413553#section=BioAssay-Results Page: 4.0	inconclusive [IC50 26.837 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/135413553#section=BioAssay-Results Page: 4.0	yes [IC50 10.684 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/135413553#section=BioAssay-Results Page: 4.0	yes [IC50 9.5221 uM]

PubMed

Title	Date	PubMed
Implication of 5-HT2 receptor subtypes in the mechanism of action of the GABAergic compound etifoxine in the four-plate test in Swiss mice.	2010-04-02	20006646
Limiting activity at beta1-subunit-containing GABAA receptor subtypes reduces ataxia.	2010-03	19940102
Etifoxine (Stresam) for chemotherapy-induced pain?	2009-12-15	19822395
Reduction and prevention of vincristine-induced neuropathic pain symptoms by the non-benzodiazepine anxiolytic etifoxine are mediated by 3alpha-reduced neurosteroids.	2009-12-15	19786322
[Lymphocytic colitis probably due to etifoxine. A case with relapse after reintroduction].	2009-09-18	19757540
General unknown screening procedure for the characterization of human drug metabolites in forensic toxicology: applications and constraints.	2009-09	19697309
Preventive and curative effects of etifoxine in a rat model of brain oedema.	2009-07	19076164
Adjustment Disorder: epidemiology, diagnosis and treatment.	2009-06-26	19558652
The anxiolytic etifoxine protects against convulsant and anxiogenic aspects of the alcohol withdrawal syndrome in mice.	2009-05	19393860
[Pathomorphosis of anxiety disorder in patients with intestinal dysbiosis].	2009	20469713
Investigation of the anticonvulsive effect of acute immobilization stress in anxious Balb/cByJ mice using GABA A-related mechanistic probes.	2008-05	18236028
[Etifoxine: a new look at the GABA receptor and anxiety].	2008-04	18826172
Neurosteroid allopregnanolone mediates anxiolytic effect of etifoxine in rats.	2007-12-12	17950705
Lack of interaction between etifoxine and CRF1 and CRF2 receptors in rodents.	2006-09	16769145
Anxiolytics, hypnotics, and antidepressants dispensed to adolescents in a French region in 2002.	2006-07	16700077
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.	2006-04	16625522
The anxiolytic etifoxine activates the peripheral benzodiazepine receptor and increases the neurosteroid levels in rat brain.	2005-12	16388839
Effects of etifoxine on stress-induced hyperthermia, freezing behavior and colonic motor activation in rats.	2004-10-15	15451655
Effects of stress and etifoxine on pentobarbital-induced loss of righting reflex in Balb/cByJ and C57BL/6J mice.	2003-12-19	14664917
[Etifoxine chlorhydrate-induced acute hepatitis].	2003-11	14732859
The modulatory effects of the anxiolytic etifoxine on GABA(A) receptors are mediated by the beta subunit.	2003-09	12871647
Effects of etifoxine on ligand binding to GABA(A) receptors in rodents.	2002-10	12354631
A double blind parallel group placebo controlled comparison of sedative and mnesic effects of etifoxine and lorazepam in healthy subjects [corrected].	2001-06	11468032
Functional modulation of gamma-aminobutyric acid(A) receptors by etifoxine and allopregnanolone in rodents.	2001-04-06	11257430
Etifoxine: evaluation of its anticonvulsant profile in mice in comparison with sodium valproate, phenytoin and clobazam.	1985	2859023

Patents

Sample Use Guides

In Vivo Use Guide

50 mg tid

Route of Administration: Oral

In Vitro Use Guide

PC12 cells were exposed to various concentrations of etifoxine (5, 10, 20, and 40 µM). Etifoxine increased neuronal-like outgrowth in PC12 cells in a dose-dependent manner

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:24:14 GMT 2025` Edited by `admin` on `Mon Mar 31 18:24:14 GMT 2025`
Record UNII	X24X82MX4X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ETIFOXINE

Official Name

English

36-801

Preferred Name

English

etifoxine [INN]

Common Name

English

HOE 36801

Code

English

HOE-36801

Code

English

Etifoxine [WHO-DD]

Common Name

English

ETIFOXINE [MI]

Common Name

English

6-CHLORO-2-ETHYLAMINO-4-METHYL-4-PHENYL-4H-3,1-BENZOXAZINE HYDROCHLORIDE

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

N05BX03