Résumés
Résumé
Le γ-hydroxybutyrate (GHB), synthétisé dans les années 1960 pour ses propriétés GABAergiques (GABA, acide γ-amino-butyrique), est une substance qui pénètre facilement et rapidement dans le cerveau. Il induit un sommeil proche du sommeil physiologique, avec un réveil de bonne qualité, et possède des indications en anesthésiologie et dans le traitement des troubles narcoleptiques et de l’addiction à l’alcool. Ses propriétés sédatives, anxiolytiques et euphorisantes ont détourné ce composé de ses indications en thérapeutique, pour une utilisation à des fins récréatives et une consommation illicite. Le GHB à doses pharmacologiques interagit avec les récepteurs GABAB cérébraux et avec une famille de récepteurs spécifiques, exprimés principalement par le système nerveux central. Cette dernière famille représente l’un des constituants essentiels d’un système GHB endogène qui aurait comme rôle principal de contrôler l’activité de certaines synapses GABA du système nerveux central.
Summary
γ-hydroxybutyrate (GHB) is mainly known because of its popularity as a drug of abuse among young individuals. However this substance increases slow-wave deep sleep and the secretion of growth hormone and besides its role in anaesthesia, it is used in several therapeutic indications including alcohol withdrawal, control of daytime sleep attacks and cataplexy in narcoleptic patients and is proposed for the treatment of fibromyalgia. GHB is also an endogenous substance present in several organs, including brain where it is synthesized from GABA in cells containing glutamic acid decarboxylase, the marker of GABAergic neurons. GHB is accumulated by the vesicular inhibitory aminoacid transporter (VIAAT) and released by depolarization via a Ca2+ dependent-mechanism. A family of GHB receptors exists in brain which possesses hyperpolarizing properties through Ca2+ and K+ channels. These receptors - one of them has been recently cloned from rat brain hippocampus - are thought to regulate GABAergic activities via a subtle balance between sensitized/desensitized states. Massive absorption of GHB desensitize GHB receptors and this modification, together with a direct stimulation of GABAB receptors by GHB, induce a perturbation in GABA, dopamine and opiate releases in several region of the brain. This adaptation phenomenon is probably responsible for the therapeutic and recreative effects of exogenous GHB.
Parties annexes
Références
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