Extrasynaptic site of action for γ-hydroxybutyrate.

A dvances in pharmacology often result from identifying the mechanism of action of drugs found empirically to be biologically active (1). γ-Hydroxybutyric acid (GHB), also known as Fantasy, is a centrally active agent that has been used clinically and recreationally for nearly half a century. Because of its history of abuse, its availability is tightly regulated, although it is prescribed for the treatment of alcoholism and narcolepsy. Depending on the dose, GHB displays a myriad of effects on CNS function. Despite decades of research, significant questions remain about its mechanism of action. In PNAS, Absalom et al. (2) identify a distinct population of extrasynaptic GABAA receptors as a target for GHB, providing unique insights into the molecular target for this agent.