| ID Source | ID |
|---|---|
| PubMed CID | 135413553 |
| CHEMBL ID | 2106227 |
| CHEBI ID | 135272 |
| SCHEMBL ID | 431973 |
| MeSH ID | M0042618 |
| Synonym |
|---|
| etifoxine |
| etifoxin |
| etifoxinum [latin] |
| 6-chloro-2-(ethylamino)-4-methyl-4-phenyl-4h-3,1-benzoxazine |
| etifoxina [inn-spanish] |
| 4h-3,1-benzoxazine, 6-chloro-2-ethylamino-4-methyl-4-phenyl- |
| brn 0548223 |
| hoe 36801 |
| etifoxina [spanish] |
| etifoxinum [inn-latin] |
| 4h-3,1-benzoxazin-2-amine, 6-chloro-n-ethyl-4-methyl-4-phenyl- |
| 2-aethylamino-6-chlor-4-methyl-4-phenyl-4h-3,1-benzoxazin [german] |
| 6-chloro-2-ethylamino-4-methyl-4-phenyl-4h-3,1-benzoxazine |
| D07320 |
| etifoxine (inn/ban) |
| 21715-46-8 |
| CHEBI:135272 |
| 6-chloro-n-ethyl-4-methyl-4-phenyl-3,1-benzoxazin-2-amine |
| hoe-36801 |
| CHEMBL2106227 |
| etifoxinum |
| etifoxine [inn:ban:dcf] |
| unii-x24x82mx4x |
| x24x82mx4x , |
| 2-aethylamino-6-chlor-4-methyl-4-phenyl-4h-3,1-benzoxazin |
| etifoxina |
| HY-16579A |
| CS-1104 |
| hoe 36-801 |
| gtpl5468 |
| 6-chloro-n-ethyl-4-methyl-4-phenyl-2,4-dihydro-1h-3,1-benzoxazin-2-imine |
| SCHEMBL431973 |
| etifoxine [who-dd] |
| etifoxine [inn] |
| etifoxine [mi] |
| 6-chloro-2-ethylamino-4-methyl-4-phenyl-4h-3,1-benzoxazine hydrochloride |
| DB08986 |
| AKOS030526117 |
| SR-01000945088-1 |
| sr-01000945088 |
| J-014253 |
| MRF-0000029 |
| Q3592452 |
| hoe36801 |
| 6-chloro-n-ethyl-4-methyl-4-phenyl-4h-benzo[d][1,3]oxazin-2-amine |
| 4692B |
| 2-(4-chlorophenyl)-3-(trifluoromethyl)pyrazole-4-carboxylicacidhydrazide |
| DTXSID00865010 |
| F81216 |
| MS-24338 |
| NCGC00350400-01 |
| 6-chloro-n-ethyl-4-methyl-4-phenyl-1h-3,1-benzoxazin-2-imine |
Etifoxine (EFX) is a non-benzodiazepine anxiolytic. It potentiates GABAA receptor (GABAAR) function directly or indirectly via the production of 3α-reduced neurosteroids. Etifoxine is a promising agent insofar as it is not associated with dependence.
| Excerpt | Reference |
|---|---|
| "Etifoxine is an anxiolytic compound with a dual mechanism of action; it is a positive allosteric modulator of GABAergic receptors as well as a ligand for the 18 kDa mitochondrial Translocator Protein (TSPO). " | ( In Vitro and In Vivo Neuroprotective Effects of Etifoxine in β-Amyloidinduced Toxicity Models. Buttigieg, D; Meunier, J; Riban, V; Verleye, M; Villard, V, 2020) |
| "Etifoxine is a clinically available anxiolytic drug, and has recently shown neuroprotective effects as a TSPO ligand." | ( TSPO ligand etifoxine attenuates LPS-induced cognitive dysfunction in mice. Guo, WZ; Hao, XM; Jiao, LB; Ma, L; Ma, YQ; Zhang, H; Zhao, HY, 2020) |
| "Etifoxine is a prescribed anxiolytic that increases GABAAA receptor function through a direct positive allosteric modulation effect and, indirectly, by stimulating the production of endogenous GABAA receptor positive modulators such as allopregnanolone-type neurosteroids." | ( The non-benzodiazepine anxiolytic etifoxine limits mechanical allodynia and anxiety-like symptoms in a mouse model of streptozotocin-induced diabetic neuropathy. Gazzo, G; Poisbeau, P; Salgado Ferrer, M, 2021) |
| "Etifoxine is a ligand of the 18-kDa translocator protein (TSPO) and has been demonstrated to serve multiple functions in nervous system." | ( Etifoxine promotes glia-derived neurite outgrowth in vitro and in vivo. Dai, T; He, B; Li, Y; Liu, X; Zheng, C; Zhou, X; Zhu, Q; Zhu, S; Zhu, Z, 2014) |
| "Etifoxine (EFX) is a non-benzodiazepine anxiolytic which potentiate GABAA receptor (GABAAR) function directly or indirectly via the production of 3α-reduced neurosteroids. " | ( Characterization of the fast GABAergic inhibitory action of etifoxine during spinal nociceptive processing in male rats. Juif, PE; Melchior, M; Poisbeau, P, 2015) |
| "Etifoxine is a promising agent insofar as it is not associated with dependence, but in primary care settings benzodiazepines continue to be frequently prescribed for psychiatric symptoms." | ( Etifoxine versus alprazolam for the treatment of adjustment disorder with anxiety: a randomized controlled trial. Stein, DJ, 2015) |
| "Etifoxine chlorhydrate is a benzoxazine derivative approved for the treatment of psychosomatic manifestations of anxiety since 1979. " | ( Safety profile of etifoxine: A French pharmacovigilance survey. Auffret, M; Bernard, N; Boulay, C; Cottin, J; Dautriche, AD; Descotes, J; Geniaux, H; Gouraud, A; Jean-Pastor, MJ; Vial, T, 2016) |
| "Etifoxine is an anxiolytic compound that belongs to the benzoxazine family." | ( Etifoxine improves sensorimotor deficits and reduces glial activation, neuronal degeneration, and neuroinflammation in a rat model of traumatic brain injury. Gauthier, D; Riban, V; Simon-O'Brien, E; Verleye, M, 2016) |
| "Etifoxine is an anxiolytic compound structurally unrelated to benzodiazepine and neurosteroids but potentiating GABA(A) receptor function by a dual mode of action including a direct positive allosteric modulation through a site distinct from that of benzodiazepines. " | ( Implication of 5-HT2 receptor subtypes in the mechanism of action of the GABAergic compound etifoxine in the four-plate test in Swiss mice. Bourin, M; Hascoët, M, 2010) |
| Excerpt | Reference |
|---|---|
| "Etifoxine has been shown to possess some anxiolytic-like effects in rodents." | ( Implication of 5-HT2 receptor subtypes in the mechanism of action of the GABAergic compound etifoxine in the four-plate test in Swiss mice. Bourin, M; Hascoët, M, 2010) |
Etifoxine treatment caused a marked reduction in the number of macrophages after cryolesion within the nerve stumps. Etifoxin pretreatment alleviated hippocampal inflammation, increased brain levels of progesterone and attenuated cognitive dysfunction in LPS-injected mice.
| Excerpt | Reference |
|---|---|
| "Etifoxine pretreatment alleviated hippocampal inflammation, increased brain levels of progesterone, allopregnanolone and attenuated cognitive dysfunction in LPS-injected mice." | ( TSPO ligand etifoxine attenuates LPS-induced cognitive dysfunction in mice. Guo, WZ; Hao, XM; Jiao, LB; Ma, L; Ma, YQ; Zhang, H; Zhao, HY, 2020) |
| "Etifoxine treatment reduced pro-inflammatory cytokines levels without affecting anti-inflammatory cytokines levels in injured rats, reduced macrophages and glial activation, and reduced neuronal degeneration." | ( Etifoxine improves sensorimotor deficits and reduces glial activation, neuronal degeneration, and neuroinflammation in a rat model of traumatic brain injury. Gauthier, D; Riban, V; Simon-O'Brien, E; Verleye, M, 2016) |
| "Etifoxine treatment caused a marked reduction in the number of macrophages after cryolesion within the nerve stumps, which was rapid in the proximal and delayed in the distal nerve stumps." | ( Etifoxine improves peripheral nerve regeneration and functional recovery. Adams, D; Baulieu, EE; Cadepond, F; Gillardin, JM; Girard, C; Lacroix, C; Liu, S; Schumacher, M; Schweizer-Groyer, G; Verleye, M, 2008) |
| Excerpt | Reference |
|---|---|
| " Previously labeled adverse drug reactions (ADRs) only include drowsiness, benign cutaneous reactions, and acute hypersensitivity reactions." | ( Safety profile of etifoxine: A French pharmacovigilance survey. Auffret, M; Bernard, N; Boulay, C; Cottin, J; Dautriche, AD; Descotes, J; Geniaux, H; Gouraud, A; Jean-Pastor, MJ; Vial, T, 2016) |
| Excerpt | Reference |
|---|---|
| " Limited human pharmacokinetic data is available for either molecule, and the binding affinity of etifoxine for human TSPO is unknown." | ( Human pharmacokinetics of XBD173 and etifoxine distinguish their potential for pharmacodynamic effects mediated by translocator protein. Aimola, L; Grey, G; Matthews, PM; Nicholas, R; O'Connor, D; Owen, DR; Phillips, A, 2022) |
| Excerpt | Reference |
|---|---|
| " Whereas vigilance, psychomotor performance and free recall were significantly impaired by lorazepam, neither dosage of etifoxine (50 and 100 mg) produced such effects." | ( A double blind parallel group placebo controlled comparison of sedative and mnesic effects of etifoxine and lorazepam in healthy subjects [corrected]. Alquier, C; Blin, O; Bruguerolle, B; Guet, F; Le Guern, ME; Micallef, J; Soubrouillard, C, 2001) |
| Class | Description |
|---|---|
| benzoxazine | |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| cytochrome P450 family 3 subfamily A polypeptide 4 | Homo sapiens (human) | Potency | 26.8370 | 0.0123 | 7.9835 | 43.2770 | AID1645841 |
| G | Vesicular stomatitis virus | Potency | 9.5221 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2D6 | Homo sapiens (human) | Potency | 10.6840 | 0.0010 | 8.3798 | 61.1304 | AID1645840 |
| Interferon beta | Homo sapiens (human) | Potency | 9.5221 | 0.0033 | 9.1582 | 39.8107 | AID1645842 |
| HLA class I histocompatibility antigen, B alpha chain | Homo sapiens (human) | Potency | 9.5221 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| Inositol hexakisphosphate kinase 1 | Homo sapiens (human) | Potency | 9.5221 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2C9, partial | Homo sapiens (human) | Potency | 9.5221 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Gamma-aminobutyric acid receptor subunit pi | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5075 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit beta-1 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5075 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit delta | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5075 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit gamma-2 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5057 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit alpha-5 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.4973 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit alpha-3 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5075 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit gamma-1 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.4988 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit alpha-2 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5046 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit alpha-4 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5075 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit gamma-3 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5075 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit alpha-6 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5075 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit alpha-1 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5065 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit beta-3 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5057 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit beta-2 | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5075 | 10.0000 | AID1551067 |
| GABA theta subunit | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5075 | 10.0000 | AID1551067 |
| Gamma-aminobutyric acid receptor subunit epsilon | Rattus norvegicus (Norway rat) | IC50 (µMol) | 6.7000 | 0.0001 | 0.5075 | 10.0000 | AID1551067 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1079932 | Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source] | |||
| AID1079948 | Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source] | |||
| AID1079933 | Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is | |||
| AID1079936 | Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source] | |||
| AID1079938 | Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source] | |||
| AID1079939 | Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source] | |||
| AID1079947 | Comments (NB not yet translated). [column 'COMMENTAIRES' in source] | |||
| AID1079934 | Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source] | |||
| AID1079931 | Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source] | |||
| AID1079941 | Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source] | |||
| AID1079937 | Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source] | |||
| AID1079942 | Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source] | |||
| AID1079940 | Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source] | |||
| AID1079949 | Proposed mechanism(s) of liver damage. [column 'MEC' in source] | |||
| AID1551067 | Displacement of [35S]TBPS from Sprague-Dawley rat brain cortical membrane GABAA receptor incubated for 90 mins by scintillation counting method | 2019 | European journal of medicinal chemistry, Jun-01, Volume: 171 | GABA allosteric modulators: An overview of recent developments in non-benzodiazepine modulators. |
| AID1079946 | Presence of at least one case with successful reintroduction. [column 'REINT' in source] | |||
| AID1079944 | Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source] | |||
| AID1079945 | Animal toxicity known. [column 'TOXIC' in source] | |||
| AID1079943 | Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source] | |||
| AID1079935 | Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source] | |||
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 4 (5.88) | 18.7374 |
| 1990's | 1 (1.47) | 18.2507 |
| 2000's | 21 (30.88) | 29.6817 |
| 2010's | 30 (44.12) | 24.3611 |
| 2020's | 12 (17.65) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 9 (12.50%) | 5.53% |
| Reviews | 4 (5.56%) | 6.00% |
| Case Studies | 2 (2.78%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 57 (79.17%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
|---|---|---|---|---|---|---|---|
| Evaluation of the Effects of Etifoxine 100 mg and Lorazepam 2 mg on Vigilance and Cognitive Functions in the Elderly. A Monocentric, Randomized, Cross-over, Double-blind Clinical Study Versus Placebo[NCT02147548] | Phase 3 | 31 participants (Actual) | Interventional | 2013-12-31 | Completed | ||
| An Experimental Medicine Study to Validate the 18 kiloDalton Translocator Protein (TSPO) as a Novel Neuroimmunodulatory Target in Multiple Sclerosis[NCT03850301] | 44 participants (Anticipated) | Interventional | 2018-04-01 | Recruiting | |||
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] | |||||||