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

Philippe Nuss,1,2 Florian Ferreri,1 Michel Bourin31Department of Adult Psychiatry and Medical Psychology, Sorbonne University, Saint-Antoine Hospital, Paris, France; 2Inserm UMR_S938, Saint-Antoine Research Centre, Sorbonne University, Paris, France; 3Department of Neurobiology of Anxiety a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nuss P, Ferreri F, Bourin M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	etifoxine adjustment disorders translocator protein18 kDa (TSPO) 3α 5α-THP (allopregnanolone) GABA benzodiazepines anxiety neuroprotection Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/524d2516a17f45f6ba7b41d57b479602
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:524d2516a17f45f6ba7b41d57b479602
record_format	dspace
spelling	oai:doaj.org-article:524d2516a17f45f6ba7b41d57b4796022021-12-02T04:47:59ZAn update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action1178-2021https://doaj.org/article/524d2516a17f45f6ba7b41d57b4796022019-07-01T00:00:00Zhttps://www.dovepress.com/an-update-on-the-anxiolytic-and-neuroprotective-properties-of-etifoxin-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Philippe Nuss,1,2 Florian Ferreri,1 Michel Bourin31Department of Adult Psychiatry and Medical Psychology, Sorbonne University, Saint-Antoine Hospital, Paris, France; 2Inserm UMR_S938, Saint-Antoine Research Centre, Sorbonne University, Paris, France; 3Department of Neurobiology of Anxiety and Depression, Faculty of Medicine, Nantes University, Nantes, FranceAbstract: 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.Keywords: etifoxine, adjustment disorders, TSPO, translocator protein 18 kDa, 3α, allopregnanolone, 5α-THP, GABA, benzodiazepines, anxiety, neuroprotectionNuss PFerreri FBourin MDove Medical Pressarticleetifoxineadjustment disorderstranslocator protein18 kDa (TSPO)3α5α-THP (allopregnanolone)GABAbenzodiazepinesanxietyneuroprotectionNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 15, Pp 1781-1795 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	etifoxine adjustment disorders translocator protein18 kDa (TSPO) 3α 5α-THP (allopregnanolone) GABA benzodiazepines anxiety neuroprotection Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	etifoxine adjustment disorders translocator protein18 kDa (TSPO) 3α 5α-THP (allopregnanolone) GABA benzodiazepines anxiety neuroprotection Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Nuss P Ferreri F Bourin M An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action
description	Philippe Nuss,1,2 Florian Ferreri,1 Michel Bourin31Department of Adult Psychiatry and Medical Psychology, Sorbonne University, Saint-Antoine Hospital, Paris, France; 2Inserm UMR_S938, Saint-Antoine Research Centre, Sorbonne University, Paris, France; 3Department of Neurobiology of Anxiety and Depression, Faculty of Medicine, Nantes University, Nantes, FranceAbstract: 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.Keywords: etifoxine, adjustment disorders, TSPO, translocator protein 18 kDa, 3α, allopregnanolone, 5α-THP, GABA, benzodiazepines, anxiety, neuroprotection
format	article
author	Nuss P Ferreri F Bourin M
author_facet	Nuss P Ferreri F Bourin M
author_sort	Nuss P
title	An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action
title_short	An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action
title_full	An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action
title_fullStr	An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action
title_full_unstemmed	An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action
title_sort	update on the anxiolytic and neuroprotective properties of etifoxine: from brain gaba modulation to a whole-body mode of action
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/524d2516a17f45f6ba7b41d57b479602
work_keys_str_mv	AT nussp anupdateontheanxiolyticandneuroprotectivepropertiesofetifoxinefrombraingabamodulationtoawholebodymodeofaction AT ferrerif anupdateontheanxiolyticandneuroprotectivepropertiesofetifoxinefrombraingabamodulationtoawholebodymodeofaction AT bourinm anupdateontheanxiolyticandneuroprotectivepropertiesofetifoxinefrombraingabamodulationtoawholebodymodeofaction AT nussp updateontheanxiolyticandneuroprotectivepropertiesofetifoxinefrombraingabamodulationtoawholebodymodeofaction AT ferrerif updateontheanxiolyticandneuroprotectivepropertiesofetifoxinefrombraingabamodulationtoawholebodymodeofaction AT bourinm updateontheanxiolyticandneuroprotectivepropertiesofetifoxinefrombraingabamodulationtoawholebodymodeofaction
_version_	1718401004523749376

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

Ejemplares similares