Carter Lawrence P, Koek Wouter, France Charles P
Clinical Research and Development, Jazz Pharmaceuticals Inc., USA.
Pharmacol Ther. 2009 Jan;121(1):100-14. doi: 10.1016/j.pharmthera.2008.10.003. Epub 2008 Oct 29.
GHB is used therapeutically and recreationally, although the precise mechanism of action responsible for its different behavioral effects is not entirely clear. The purpose of this review is to summarize how behavioral procedures, especially drug discrimination procedures, have been used to study the mechanism of action of GHB. More specifically, we will review several different drug discrimination procedures and discuss how they have been used to qualitatively and quantitatively study different components of the complex mechanism of action of GHB. A growing number of studies have provided evidence that the behavioral effects of GHB are mediated predominantly by GABAB receptors. However, there is also evidence that the mechanisms mediating the effects of GHB and the prototypical GABAB receptor agonist baclofen are not identical, and that other mechanisms such as GHB receptors and subtypes of GABAA and GABAB receptors might contribute to the effects of GHB. These findings are consistent with the different behavioral profile, abuse liability, and therapeutic indications of GHB and baclofen. A better understanding of the similarities and differences between GHB and baclofen, as well as the pharmacological mechanisms of action underlying the recreational and therapeutic effects of GHB, could lead to more effective medications with fewer adverse effects.
γ-羟基丁酸（GHB）被用于治疗和娱乐用途，尽管其产生不同行为效应的确切作用机制尚不完全清楚。本综述的目的是总结行为学方法，特别是药物辨别程序，如何被用于研究GHB的作用机制。更具体地说，我们将回顾几种不同的药物辨别程序，并讨论它们如何被用于定性和定量研究GHB复杂作用机制的不同组成部分。越来越多的研究提供了证据表明，GHB的行为效应主要由GABAB受体介导。然而，也有证据表明，介导GHB效应的机制与典型的GABAB受体激动剂巴氯芬并不相同，并且其他机制，如GHB受体以及GABAA和GABAB受体的亚型可能也对GHB的效应有贡献。这些发现与GHB和巴氯芬不同的行为特征、滥用可能性及治疗指征相一致。更好地理解GHB和巴氯芬之间的异同，以及GHB娱乐和治疗作用背后的药理作用机制，可能会带来更有效且副作用更少的药物。
