Pharmacological Effects and Toxicology of Gamma-Hydroxybutyrate
Summary
Gamma-hydroxybutyrate (GHB) is a central nervous system depressant with both clinical and illicit applications. Clinically, its sodium salt is approved for narcolepsy-associated cataplexy and, in some regions, for alcohol‐dependence treatment. Pharmacologically, GHB acts as an agonist at GABAB receptors and binds a distinct high‐affinity GHB receptor, producing sedative, hypnotic and euphoric effects. Uptake and elimination follow nonlinear kinetics, largely mediated by monocarboxylate transporters, leading to dose‐dependent saturation of metabolism and renal reabsorption. Toxicologically, GHB has a narrow therapeutic index: modest increases in dose can precipitate profound respiratory depression, coma and bradycardia, particularly when combined with alcohol or other central depressants. Chronic use may induce tolerance, dependence and a characteristic withdrawal syndrome marked by rapid onset of agitation, tremor, delirium and autonomic instability. Analytical detection is challenged by rapid metabolism to endogenous metabolites and a short detection window in common matrices. Forensic and clinical concerns have driven research into improved detection methods, therapeutic strategies for overdose and withdrawal management, and an understanding of neuroadaptive changes following repeated exposure.
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Pharmacological Effects and Toxicology of Gamma-Hydroxybutyrate publication trend
The graph below shows the total number of articles in pharmacological effects and toxicology of gamma-hydroxybutyrate across all publications each year (not limited to Nature Index journals).
Technical terms
Monocarboxylate transporter 1 (MCT1): A membrane protein mediating cellular influx and efflux of monocarboxylates, including GHB, thereby shaping its absorption, distribution and elimination.
Toxicokinetics: The study of how a substance is absorbed, distributed, metabolised and excreted in the body, particularly at toxic doses.
Toxicodynamics: The examination of the biochemical and physiological effects of toxic substances and the mechanisms through which these effects occur.
GABAB receptor: A G‐protein-coupled receptor for γ-aminobutyric acid that mediates the principal inhibitory actions of GHB in the central nervous system.
References
- Sex and Cross-Sex Testosterone Treatment Alters Gamma-Hydroxybutyrate Acid Toxicokinetics and Toxicodynamics in Rats. Pharmaceutics (2024).
- Pharmacological Treatment of GHB Withdrawal Syndrome. Current Addiction Reports (2024).
- Effect of Repeated Administration of ɣ-Valerolactone (GVL) and GHB in the Mouse: Neuroadaptive Changes of the GHB and GABAergic System. Pharmaceuticals (2023).
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