Etifoxine
(Synonyms: 艾替伏辛,HOE 36-801) 目录号 : GC36012
A positive allosteric modulator of GABAA receptors
Cas No.:21715-46-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Etifoxine is a positive allosteric modulator of α1β2γ2 and α1β3γ2 subunit-containing GABAA receptors.1 It selectively increases GABA-induced currents in X. laevis oocytes expressing α1β2γ2 or α1β3γ2 over α1β1γ2 subunit-containing receptors at 20 ?M. Etifoxine inhibits binding of the GABAA receptor agonist muscimol in rat corticol membranes with a Kd value of 23 nM in a radioligand binding assay.2 It increases NGF-induced neurite outgrowth in PC12 cells when used at a concentration of 20 ?M.3 Etifoxine (12.5 mg/kg, i.p.) increases the percentage of time spent in the open arms of the elevated plus maze in high-anxiety BALB/cByJ, but not C57BL/6, mice, indicating anxiolytic-like activity.4 It increases the seizure threshold in a mouse model of seizures induced by picrotoxin with a minimum effective dose (MED) of 75 mg/kg.2 Etifoxine (50 mg/kg, i.p.) also increases the paw withdrawal threshold on the ipsilateral side in a rat model of rheumatoid arthritis induced by complete Freund's adjuvant.5
1.Hamon, A., Morel, A., Hue, B., et al.The modulatory effects of the anxiolytic etifoxine on GABAA receptors are mediated by the β subunitNeuropharmacology45(3)293-303(2003) 2.Verleye, M., Pansart, Y., and Gillardin, J.Effects of etifoxine on ligand binding to GABAA receptors in rodentsNeurosci. Res.44(2)167-172(2002) 3.Girard, C., Liu, S., Cadepond, F., et al.Etifoxine improves peripheral nerve regeneration and functional recoveryProc. Natl. Acad. Sci. USA105(51)20505-20510(2008) 4.Verleye, M., Dumas, S., Heulard, I., et al.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.21(6)457-470(2011) 5.Aouad, M., Zell, V., Juif, P.E., et al.Etifoxine analgesia in experimental monoarthritis: A combined action that protects spinal inhibition and limits central inflammatory processesPain155(2)403-412(2014)
| Cas No. | 21715-46-8 | SDF | |
| 别名 | 艾替伏辛,HOE 36-801 | ||
| Canonical SMILES | ClC1=CC=C2C(C(C3=CC=CC=C3)(C)OC(NCC)=N2)=C1 | ||
| 分子式 | C17H17ClN2O | 分子量 | 300.78 |
| 溶解度 | DMSO: 100 mg/mL (332.47 mM) | 储存条件 | Store at -20°C |
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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 |
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Etifoxine for pain patients with anxiety
Korean J Pain 2015 Jan;28(1):4-10.PMID:25589941DOI:10.3344/kjp.2015.28.1.4.
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 GABAAα2 receptors like benzodiazepines, Etifoxine appears to produce anxiolytic effects directly by binding to β2 or β3 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. It potentiates GABAA receptor-function by a direct allosteric effect and by an indirect mechanism involving the activation of TSPO. It seems promising that non-benzodiazepine anxiolytics including Etifoxine will replenish shortcomings of benzodiazepines and selective serotonin reuptake inhibitors according to animated studies related to TSPO.
Translocator Protein Ligand Etifoxine Attenuates MPTP-Induced Neurotoxicity
Front Mol Neurosci 2022 May 24;15:850904.PMID:35686060DOI:10.3389/fnmol.2022.850904.
Parkinson's disease (PD) is a neurodegenerative disease, but the currently available treatments for this disease are symptomatic treatments. There is evidence that translocator protein (18 kDa) (TSPO) expression is upregulated in some neurodegenerative diseases, and TSPO ligands have obvious neuroprotective effects. However, the neuroprotective effects and other potential effects of the TSPO ligand Etifoxine in PD remain unclear. Therefore, the present study was designed to explore the impacts of Etifoxine on a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We found that Etifoxine significantly reduced motor function deficits, decreased the loss of tyrosine hydroxylase-positive neurons in the substantia nigra, and attenuated the decrease in striatal dopamine levels in mice that received MPTP. Etifoxine diminished the production of inflammatory mediators and infiltration of leukocytes in the brain after MPTP exposure. In vitro studies suggested that microglia contribute to Etifoxine's neuroprotective effect. The results showed that Etifoxine can alleviate MPTP-induced neurotoxicity and neuroinflammation, providing a new idea for the treatment of PD.
An update on the anxiolytic and neuroprotective properties of Etifoxine: from brain GABA modulation to a whole-body mode of action
Neuropsychiatr Dis Treat 2019 Jul 3;15:1781-1795.PMID:31308671DOI:10.2147/NDT.S200568.
Treating the signs and symptoms of anxiety is an everyday challenge in clinical practice. When choosing between treatment options, anxiety needs to be understood in the situational, psychiatric, and biological context in which it arises. Etifoxine, a non-benzodiazepine anxiolytic drug belonging to the benzoxazine class, is an effective treatment for anxiety in response to a stressful situation. In the present review, we focused on several aspects of the cerebral and somatic biological mechanisms involved in anxiety and investigated the extent to which Etifoxine's mode of action can explain its anxiolytic activity. Its two mechanisms of action are the modulation of GABAergic neurotransmission and neurosteroid synthesis. Recent data suggest that the molecule possesses neuroprotective, neuroplastic, and anti-inflammatory properties. Etifoxine was first shown to be an effective anxiolytic in patients in clinical studies comparing it with clobazam, sulpiride, and placebo. Randomized controlled studies have demonstrated its anxiolytic efficacy in patients with adjustment disorders (ADs) with anxiety, showing it to be superior to buspirone and comparable to lorazepam and phenazepam, with a greater number of markedly improved responders and a better therapeutic index. Etifoxine's noninferiority to alprazolam has also been demonstrated in a comparative trial. Significantly less rebound anxiety was observed after abrupt cessation of Etifoxine compared with lorazepam or alprazolam. Consistent with this finding, Etifoxine appears to have a very low dependence potential. Unlike lorazepam, it has no effect on psychomotor performance, vigilance, or free recall. Severe adverse events are in general rare. Skin and subcutaneous disorders are the most frequently reported, but these generally resolve after drug cessation. Taken together, its dual mechanisms of action in anxiety and the positive data yielded by clinical trials support the use of Etifoxine for treating the anxiety signs and symptoms of individuals with ADs.
Etifoxine Restores Mitochondrial Oxidative Phosphorylation and Improves Cognitive Recovery Following Traumatic Brain Injury
Int J Mol Sci 2021 Nov 28;22(23):12881.PMID:34884686DOI:10.3390/ijms222312881.
The opening of the mitochondrial permeability transition pore (mPTP) has emerged as a pivotal event following traumatic brain injury (TBI). Evidence showing the impact of the translocator protein (TSPO) over mPTP activity has prompted several studies exploring the effect of TSPO ligands, including Etifoxine, on the outcome of traumatic brain injury (TBI). Mitochondrial respiration was assessed by respirometry in isolated rat brain mitochondria (RBM) by measurements of oxidative phosphorylation capacity (OXPHOS). The addition of calcium to RBM was used to induce mitochondrial injury and resulted in significant OXPHOS reduction that could be reversed by preincubation of RBM with Etifoxine. Sensorimotor and cognitive functions were assessed following controlled cortical impact and compared in vehicle and etifoxine-treated animals. There was no difference between the vehicle and Etifoxine groups for sensorimotor functions as assessed by rotarod. In contrast, Etifoxine resulted in a significant improvement of cognitive functions expressed by faster recovery in Morris water maze testing. The present findings show a significant neuroprotective effect of Etifoxine in TBI through restoration of oxidative phosphorylation capacity associated with improved behavioral and cognitive outcomes. Since Etifoxine is a registered drug used in common clinical practice, implementation in a phase II study may represent a reasonable step forward.
TSPO ligand Etifoxine attenuates LPS-induced cognitive dysfunction in mice
Brain Res Bull 2020 Dec;165:178-184.PMID:33075418DOI:10.1016/j.brainresbull.2020.10.013.
The translocator protein (TSPO), once known as peripheral-type benzodiazepine receptor, was reported to be related with several physiological functions. Etifoxine is a clinically available anxiolytic drug, and has recently shown neuroprotective effects as a TSPO ligand. The aim of the present study was to investigate the influence of Etifoxine on LPS-induced neuroinflammation and cognitive dysfunction. C57/BL6 male mice were injected with Etifoxine (50 mg/kg, i.p.) three days before lipopolysaccharide (LPS, 500 μg/kg, i.p.) administration. Etifoxine pretreatment alleviated hippocampal inflammation, increased brain levels of progesterone, allopregnanolone and attenuated cognitive dysfunction in LPS-injected mice. While LPS increased expression of caspase-3 and decreased p-Akt/Akt, Etifoxine returned caspase-3 and p-Akt/Akt to control levels. Finasteride, a 5α-reductase inhibitor that blocked allopregnanolone production, partially reversed the effects of Etifoxine. We concluded that Etifoxine exerted neuroprotective effects in LPS-induced neuroinflammation and the neuroprotection may be related with increase of neurosteroids synthesis and decrease of apoptosis.