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Review
. 2016 May;36(3):363-88.
doi: 10.1002/med.21382. Epub 2016 Jan 6.

Mechanisms for the Specific Properties of γ-Hydroxybutyrate in Brain

Michel Maitre  1 , Christian Klein  1 , Ayikoe G Mensah-Nyagan  1
Affiliations
Review

Mechanisms for the Specific Properties of γ-Hydroxybutyrate in Brain

Michel Maitre et al. Med Res Rev. 2016 May.

Abstract

γ-Hydroxybutyrate (GHB) is both a natural brain compound with neuromodulatory properties at central GABAergic synapses (micromolar concentration range) and also a drug (Xyrem(R) ) clinically used for the treatment of various neurological symptoms (millimolar dose range). However, this drug has abuse potential and can be addictive for some patients. Here, we review the basic mechanistic role of endogenous GHB in brain as well as the properties and mechanisms of action for therapeutic clinical doses of exogenous GHB. Several hypotheses are discussed with a preference for a molecular mechanism that conciliates most of the findings available. This conciliatory model may help for the design of GHB-like drugs active at lower doses and devoid of major side effects.

Keywords: GHB; gamma-hydroxybutyrate; mechanisms of action; therapeutic doses; xyrem.

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