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- W2149964058 abstract "gamma-Hydroxybutyric acid (GHB) is an endogenous neurotransmitter that is abused because of its sedative/hypnotic and euphoric effects. The objectives of this study were to evaluate the concentration-effect relationships of GHB in plasma, cerebrospinal fluid (CSF), brain (whole and discrete brain regions), and brain frontal cortex extracellular fluid. This information is crucial for future studies to evaluate effects of therapeutic interventions on the toxicodynamics of GHB. GHB (200-1000 mg/kg) was administered intravenously to rats, and plasma and frontal cortex microdialysate samples were collected for up to 6 h after the dose, or plasma, CSF, and brain (whole, frontal cortex, striatum, and hippocampus) concentrations were determined at the offset of its sedative/hypnotic effect [return to righting reflex (RRR)]. GHB-induced changes in the brain neurotransmitters gamma-aminobutyric acid (GABA) and glutamate were also determined. GHB, GABA, and glutamate concentrations were measured by liquid chromatography/tandem mass spectrometry. GHB-induced sleep time significantly increased in a dose-dependent manner (20-fold increase from 200 to 1000 mg/kg). GHB concentrations in plasma (300-400 microg/ml), whole brain (70 microg/g), discrete brain regions (80-100 microg/g), and brain microdialysate (29-39 microg/ml) correlated with RRR. In contrast, CSF GHB and GABA and glutamate concentrations in discrete brain regions exhibited no relationship with RRR. Our results suggest that GHB-induced sedative/hypnotic effects are mediated directly by GHB and that at high GHB doses, GABA formation from GHB may not contribute to the observed sedative/hypnotic effect. These results support the use of a clinical GHB detoxification strategy aimed at decreasing plasma and brain GHB concentrations after GHB overdoses." @default.
- W2149964058 created "2016-06-24" @default.
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- W2149964058 date "2010-03-09" @default.
- W2149964058 modified "2023-09-25" @default.
- W2149964058 title "Concentration-Effect Relationships for the Drug of Abuse γ-Hydroxybutyric Acid" @default.
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- W2149964058 doi "https://doi.org/10.1124/jpet.109.165381" @default.
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