The non-benzodiazepine anxiolytic drug etifoxine causes a rapid, receptor-independent stimulation of neurosteroid biosynthesis

PloS One
Jean Luc Do RegoH Vaudry

Abstract

Neurosteroids can modulate the activity of the GABAA receptors, and thus affect anxiety-like behaviors. The non-benzodiazepine anxiolytic compound etifoxine has been shown to increase neurosteroid concentrations in brain tissue but the mode of action of etifoxine on neurosteroid formation has not yet been elucidated. In the present study, we have thus investigated the effect and the mechanism of action of etifoxine on neurosteroid biosynthesis using the frog hypothalamus as an experimental model. Exposure of frog hypothalamic explants to graded concentrations of etifoxine produced a dose-dependent increase in the biosynthesis of 17-hydroxypregnenolone, dehydroepiandrosterone, progesterone and tetrahydroprogesterone, associated with a decrease in the production of dihydroprogesterone. Time-course experiments revealed that a 15-min incubation of hypothalamic explants with etifoxine was sufficient to induce a robust increase in neurosteroid synthesis, suggesting that etifoxine activates steroidogenic enzymes at a post-translational level. Etifoxine-evoked neurosteroid biosynthesis was not affected by the central-type benzodiazepine (CBR) receptor antagonist flumazenil, the translocator protein (TSPO) antagonist PK11195 or the GABA...Continue Reading

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Citations

Jul 23, 2015·The Journal of Steroid Biochemistry and Molecular Biology·B D ArboM F Ribeiro
Jul 17, 2016·The Journal of Endocrinology·Vimal Selvaraj, Lan N Tu
Sep 12, 2018·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Pierrick PoisbeauLaurent Calvel
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Jun 2, 2020·CNS & Neurological Disorders Drug Targets·Veronique RibanMarc Verleye
Jul 10, 2019·Pharmacology & Therapeutics·Marie-Christine TononJérôme Leprince
Oct 22, 2017·Neuroscience and Biobehavioral Reviews·Tatiana BarichelloJoao Quevedo
Jun 29, 2018·Pharmacology & Therapeutics·Marina SchvererIsabelle Villey

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