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Etifoxine

MeDieViL

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Feb 11, 2007
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Etifoxine (INN, also known as etafenoxine; trade name Stresam) is an anxiolytic and anticonvulsant drug.[3] It is used in anxiety disorders and to promote peripheral nerve healing.[4] It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic.[5] It is more effective than lorazepam as an anxiolytic, and has fewer side effects.[6]
Etifoxine has been associated with acute liver injury.[1]
[edit]Mechanism of action

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.[7] This difference in binding means that etifoxine can be used alongside benzodiazepines to potentiate their effects without competing for binding sites,[8] however it also means that the effects of etifoxine are not reversed by the benzodiazepine antagonist flumazenil.[9]

http://en.wikipedia.org/wiki/Etifoxine

Looks interesting..
Any experiences?
 
While its not a benzodiazepine, there are certainly some similarities....

Never heard of it before...
 
No personal experience on my side.

But it's an interesting structure though. Neuropharmacol 2003, 45(3), p.293 states that for its action mainly beta2- & beta3-containing GABAA-receptors are responsible, less pronounced with beta1 as well. That is quite contrary to benzodiazepine's binding site (alpha+gamma). Neurosteroid's binding site is also excluded in the said article, as is the barbiturate-site.

The authors suggest a by now hardly discussed binding site, hidden in the intracellular part of the receptor and located in predominantly in beta2-subunits. Compounds with similar (equal?) mechanism of action that are discussed are loreclezole, etomidate an mefenamic acid. Any insinght into the action of these agents will probably provide a better view on etifoxine as well.

Peace! - Murphy
 
The anxiolytic etifoxine protects against convulsant and anxiogenic aspects of the alcohol withdrawal syndrome in mice.

Verleye M, Heulard I, Gillardin JM.
Biocodex-Département de Pharmacologie-Zac de Mercières, Compiègne, France. [email protected]
Change in the function of gamma-aminobutyric acid(A) (GABA(A)) receptors attributable to alterations in receptor subunit composition is one of main molecular mechanisms with those affecting the glutamatergic system which accompany prolonged alcohol (ethanol) intake. These changes explain in part the central nervous system hyperexcitability consequently to ethanol administration cessation. Hyperexcitability associated with ethanol withdrawal is expressed by physical signs, such as tremors, convulsions, and heightened anxiety in animal models as well as in humans. The present work investigated the effects of anxiolytic compound etifoxine on ethanol-withdrawal paradigms in a mouse model. The benzodiazepine diazepam was chosen as reference compound. Ethanol was given to NMRI mice by a liquid diet at 3% for 8 days, then at 4% for 7 days. Under these conditions, ethanol blood level ranged between 0.5 and 2 g/L for a daily ethanol intake varying from 24 to 30 g/kg. These parameters permitted the emergence of ethanol-withdrawal symptoms once ethanol administration was terminated. Etifoxine (12.5-25 mg/kg) and diazepam (1-4 mg/kg) injected intraperitoneally 3h 30 min after ethanol removal, decreased the severity in handling-induced tremors and convulsions in the period of 4-6h after withdrawal from chronic ethanol treatment. In addition when administered at 30 and 15 min, respectively, before the light and dark box test, etifoxine (50mg/kg) and diazepam (1mg/kg) inhibited enhanced aversive response 8h after ethanol withdrawal. Etifoxine at 25 and 50 mg/kg doses was without effects on spontaneous locomotor activity and did not exhibit ataxic effects on the rota rod in animals not treated with ethanol. These findings demonstrate that the GABAergic compound etifoxine selectively reduces the physical signs and anxiety-like behavior associated with ethanol withdrawal in a mouse model and may hold promise in the treatment of ethanol-withdrawal syndrome in humans.

Preventive and curative effects of etifoxine in a rat model of brain oedema.

Girard P, Pansart Y, Gillardin JM.
Biocodex, Pharmacology Department, Zac de Mercières, Compiègne, France. [email protected]
1. The aim of the present study was to test the hypothesis that increasing GABAergic neurotransmission is involved in the prevention or treatment of brain oedema. The study was conducted in the well-established rat triethyltin (TET) model of brain oedema and examined the effects of etifoxine, a compound that increases GABAergic neurotransmission through multiple mechanisms, including neurosteroid synthesis. 2. Daily oral administration of 3 mg/kg per day TET for 5 consecutive days strongly perturbed rat behaviour and induced reproducible cerebral oedema. Coadministration of etifoxine (2 x 25 or 2 x 50 mg/kg per day, p.o.) over the 5 days of TET treatment blocked the development of brain oedema and the increase in brain sodium content induced by TET, as well as reducing the increase in brain chloride content. Moreover, etifoxine inhibited the decrease in bodyweight, the neurological deficit and the altered locomotor activity induced by TET. At a lower dose (2 <--> 10 mg/kg per day, p.o.), etifoxine did not have any preventive effects. 3. To examine the curative effects of etifoxine, it was administered from the 4th day of TET treatment for 5 consecutive days, when brain oedema was already established. In these experiments, etifoxine (2 <--> 50 mg/kg per day, p.o.) significantly reduced cerebral oedema and the outcomes induced by TET treatment. Moreover, etifoxine reduced the mortality in response to TET treatment. 4. In conclusion, because etifoxine has a good safety profile as an anxiolytic, the results of the present study suggest that it is worth further clinical investigation as a neuroprotectant.

Etifoxine improves peripheral nerve regeneration and functional recovery.

Girard C, Liu S, Cadepond F, Adams D, Lacroix C, Verleye M, Gillardin JM, Baulieu EE, Schumacher M, Schweizer-Groyer G.
Unité Mixte de Recherche 788, Institut National de la Santé et de la Recherche Médicale, and Université Paris-Sud 11, 94276 Le Kremlin-Bicêtre Cedex, France.
Peripheral nerves show spontaneous regenerative responses, but recovery after injury or peripheral neuropathies (toxic, diabetic, or chronic inflammatory demyelinating polyneuropathy syndromes) is slow and often incomplete, and at present no efficient treatment is available. Using well-defined peripheral nerve lesion paradigms, we assessed the therapeutic usefulness of etifoxine, recently identified as a ligand of the translocator protein (18 kDa) (TSPO), to promote axonal regeneration, modulate inflammatory responses, and improve functional recovery. We found by histologic analysis that etifoxine therapy promoted the regeneration of axons in and downstream of the lesion after freeze injury and increased axonal growth into a silicone guide tube by a factor of 2 after nerve transection. Etifoxine also stimulated neurite outgrowth in PC12 cells, and the effect was even stronger than for specific TSPO ligands. 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. Functional tests revealed accelerated and improved recovery of locomotion, motor coordination, and sensory functions in response to etifoxine. This work demonstrates that etifoxine, a clinically approved drug already used for the treatment of anxiety disorders, is remarkably efficient in promoting acceleration of peripheral nerve regeneration and functional recovery. Its possible mechanism of action is discussed, with reference to the neurosteroid concept. This molecule, which easily enters nerve tissues and regulates multiple functions in a concerted manner, offers promise for the treatment of peripheral nerve injuries and axonal neuropathies.

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.

Nguyen N, Fakra E, Pradel V, Jouve E, Alquier C, Le Guern ME, Micallef J, Blin O.
CPCET et Pharmacologie Clinique, Institut des Neurosciences Cognitives de la Méditerranée, Faculté de Médecine, UMR CNRS Université de la Méditerranée, Assistance Publique Hôpitaux de Marseille-Hôpital de la Timone, 13385 Marseille Cedex 5, France.
Adjustment Disorders With Anxiety (ADWA) account for almost 10% of psychologically motivated consultations in primary care. The aim of this double-blind randomised parallel group study was to compare (non-inferiority test) the efficacies of etifoxine, a non-benzodiazepine anxiolytic drug, and lorazepam, a benzodiazepine, for ADWA outpatients followed by general practitioners. 191 outpatients (mean age: 43, female: 66%) were assigned to receive etifoxine (50 mg tid) or lorazepam (0.5-0.5-1 mg /day) for 28 days. Efficacy was evaluated on days 7 and 28 of the treatment. The main efficacy assessment criterion was the Hamilton Rating Scale for Anxiety score (HAM-A) on Day 28 adjusted to Day 0. The anxiolytic effect of etifoxine was found not inferior to that of lorazepam (HAM-A score decrease: 54.6% vs 52.3%, respectively, p=0.0006). The two drugs were equivalent on Day 28. However, more etifoxine recipients responded to the treatment (HAM-A score decreased by >or=50%, p=0.03). Clinical improvement (based on Clinical Global Impression scale CGI, Social Adjustment Scale Self-Report SAS-SR, and Sheehan scores) was observed in both treatment arms, but more etifoxine patients improved markedly (p=0.03) and had a marked therapeutic effect without side effects as assessed by CGI, p=0.04. Moreover, 1 week after stopping treatment, fewer patients taking etifoxine experienced a rebound of anxiety, compared to lorazepam (1 and 8, respectively, p=0.034). Copyright (c) 2006 John Wiley & Sons, Ltd.

I might go to france to get a script, i'm from belguim so its not too far;)
 
Seriously, bump.

I'm surprised there's not much to be found on BL regarding etifoxine. I'm on some right now. Takes a while to really kick in compared to most benzo's I've taken (not a whole lot). First effects noted at 10-15 minutes, warm, bit tingly feeling, but actual anxiolytic effects took hold after approximately an hour. It's only the first time I took it, but I think prefer this stuff over benzo's, it doesn't knock me out as much. Not everything French sucks ass apparently.

And while my rambling above lacks any scientific value, I'll just post the full paper on etifoxine's effects on "peripheral nerve regeneration and functional recovery" to make up for that.
http://www.pnas.org/content/105/51/20505.full
 
I have tried it last year, was trying in the "junkie mode" ate 5 or 6 capsules and had no any anxiolysis but bad headache and a little bit sleepy.
 
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