Etifoxine Promotes Glia-Derived Neurite Outgrowth In Vitro and In Vivo

Dai, Ting; Zhou, Xiang; Li, Yanan; He, Bo; Zhu, Zhaowei; Zheng, Canbin; Zhu, Shuang; Zhu, Qian; Liu, Xiaolin

doi:10.1055/s-0034-1381751

Cited by 8 publications

(2 citation statements)

References 24 publications

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“…Etifoxine, as a ligand of the TSPO, is proven to promote axonal regeneration, to modulate inflammatory response, and to improve functional recovery since 2008 [ 18 , 19 ]. It also stimulates neurite outgrowth and glia-derived neurite outgrowth [ 20 , 21 ]. Therefore, it provides benefits in nerve repair with acelluar nerve grafts [ 22 ].…”

Section: Action Mechanisms For Periperal Nerve Healing and Regeneratimentioning

confidence: 99%

Etifoxine for Pain Patients with Anxiety

Choi

Kim

2015

Korean J Pain

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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.

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Section: Action Mechanisms For Periperal Nerve Healing and Regeneratimentioning

confidence: 99%

Etifoxine for Pain Patients with Anxiety

Choi

Kim

2015

Korean J Pain

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“…Dai et al, showed that etifoxine increases neuronal-like outgrowth in PC-12 cells in a concentration-dependent manner. They also demonstrated that etifoxine improves sciatic nerve regeneration, modulates immune responses, and boosts neurotrophin expression 70. In a rat acellular nerve allograft model (for treating peripheral nerve injury), Zhou et al, reported that etifoxine increased the expression of neurofilaments in regenerated axons, improving sciatic nerve regeneration, increasing nerve conduction velocity, improving walking behaviors, and increasing neurotrophin expression 69…”

Section: Neuroprotective Activity Of Etifoxine In the Central And Permentioning

confidence: 99%

<p>An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action</p>

Nuss¹,

Ferreri²,

Bourin³

2019

NDT

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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.

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Effect of Induction Time on the Proliferation and Differentiation of Induced Schwann-Like Cells from Adipose-Derived Stem Cells

Wong

Liu

et al. 2020

Cell Mol Neurobiol

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To compare how different induction time takes effect on the proliferation and secretion ability of adipose-derived stem cell (ADSC)-induced Schwann-like cells (iSCs), ADSCs were isolated from healthy adult female rats. Flow cytometry (FCM) was performed to detect the ADSC-positive markers CD29, CD44, and CD90 and the negative marker CD45. iSC induction medium was used to culture the ADSCs. S-100, GFAP, MBP, and P75 were detected by immunofluorescence staining to identify iSC differentiation. Cell morphological changes were observed by an inverted microscope after induction. An MTS assay was used to evaluate the cell proliferation ability. Western blot analyses of caspase-3/cleaved caspase-3 and FCM were applied to assess cell apoptosis. Co-culture system of PC12 and ADSCs or iSCs was established to analyse the biological function of iSCs. Among the examined proteins, S-100, GFAP, MBP, and P75 were expressed in iSCs. After day 7, the cell proliferation rate was significantly lower than that before induction, and on day 19, the proliferation rate of iSCs was lower than 50% of the proliferation rate before induction (OD value = 0.016 ± 0.003 vs. 0.400 ± 0.004, p < 0.01). Starting from day 19, P21, P53, Apoj, S100, Gdnf, and Mbp all consistently showed a trend toward increased expression. Secretion of NGF, MBP, and BDNF was more enhanced at 19 days than that at 7 days. In co-culture system, the induction effect of iSCs was more pronounced at 19 days than that at 7 days, and the difference was statistically significant (55.40 ± 4.50 μm vs 37.15 ± 3.75 μm, p < 0.01). In conclusion, the proliferation ability of ADSC-derived iSCs was negatively correlated with the induction time, while the expression of SC marker proteins was positively correlated. Therefore, iSCs are suitable for use at 19 days after induction.

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Etifoxine Promotes Glia-Derived Neurite Outgrowth In Vitro and In Vivo

Abstract: Because of etifoxine's adverse effects, we suggest an optimal etifoxine concentration of 20 µM. Its beneficial role may lie in increased neurotrophin expression, and etifoxine may be a promising therapeutic for patients with peripheral nerve injuries.

Cited by 8 publications

References 24 publications

Etifoxine for Pain Patients with Anxiety

Etifoxine for Pain Patients with Anxiety

<p>An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action</p>

Effect of Induction Time on the Proliferation and Differentiation of Induced Schwann-Like Cells from Adipose-Derived Stem Cells

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