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Mechanisms for the Specific Properties of γ-Hydroxybutyrate in Brain
Michel Maitre1, Christian Klein1, Ayikoe G Mensah-Nyagan1
1Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Bâtiment 3 de la Faculté de Médecine, 11 rue Humann, 67000, Strasbourg, France.
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.
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