Biopathologie 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.
Med Res Rev. 2016 May;36(3):363-88. doi: 10.1002/med.21382. Epub 2016 Jan 6.
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.
γ-羟基丁酸（GHB）既是一种天然的脑内化合物，在中枢 GABA 能突触具有神经调节特性（微摩尔浓度范围），也是一种临床上用于治疗各种神经症状的药物（Xyrem（R））（毫摩尔剂量范围）。然而，这种药物有滥用的潜力，对一些患者可能会上瘾。在这里，我们回顾了内源性 GHB 在大脑中的基本作用机制，以及外源性 GHB 的治疗临床剂量的特性和作用机制。讨论了几种假说，其中更倾向于一种可以调和大多数现有发现的分子机制。这种调和模型可能有助于设计在较低剂量下具有活性且没有主要副作用的类似 GHB 的药物。
