GHB (-Hydroxybutyrate) Carrier-Mediated Transport across the Blood-Brain Barrier

-Hydroxybutyrate (sodium oxybate, GHB) is an approved ther-apeutic agent for cataplexy with narcolepsy. GHB is widely abused as an anabolic agent, euphoriant, and date rape drug. Recreational abuse or overdose of GHB (or its precursors -bu-tyrolactone or 1,4-butanediol) results in dose-dependent cen-tral nervous system (CNS) effects (respiratory depression, un-consciousness, coma, and death) as well as tolerance and withdrawal. An understanding of the CNS transport mecha-nisms of GHB may provide insight into overdose treatment approaches. The hypothesis that GHB undergoes carrier-me-diated transport across the BBB was tested using a rat in situ brain perfusion technique. Various pharmacological agents were used to probe the pharmacological characteristics of the transporter. GHB exhibited carrier-mediated transport acros