ABSTRACT
Gamma-hydroxybutyrate (GHB) is a short-chain fatty acid present endogenously in the brain and used therapeutically for the treatment of narcolepsy, as sodium oxybate, and for alcohol abuse/withdrawal. GHB is better known however as a drug of abuse and is commonly referred to as the "date-rape drug"; current use in popular culture includes recreational "chemsex," due to its properties of euphoria, loss of inhibition, amnesia, and drowsiness. Due to the steep concentration-effect curve for GHB, overdoses occur commonly and symptoms include sedation, respiratory depression, coma, and death. GHB binds to both GHB and GABAB receptors in the brain, with pharmacological/toxicological effects mainly due to GABAB agonist effects. The pharmacokinetics of GHB are complex and include nonlinear absorption, metabolism, tissue uptake, and renal elimination processes. GHB is a substrate for monocarboxylate transporters, including both sodium-dependent transporters (SMCT1, 2; SLC5A8; SLC5A12) and proton-dependent transporters (MCT1-4; SLC16A1, 7, 8, and 3), which represent significant determinants of absorption, renal reabsorption, and brain and tissue uptake. This review will provide current information of the pharmacology, therapeutic effects, and pharmacokinetics/pharmacodynamics of GHB, as well as therapeutic strategies for the treatment of overdoses. Graphical abstract.
Subject(s)
Drug Overdose/therapy , Hydroxybutyrates/pharmacokinetics , Sodium Oxybate/pharmacokinetics , Substance Abuse, Oral/therapy , Alcoholism/complications , Alcoholism/drug therapy , Animals , Disease Models, Animal , Drug Evaluation, Preclinical , Drug Overdose/etiology , Humans , Hydroxybutyrates/administration & dosage , Hydroxybutyrates/toxicity , Metabolic Clearance Rate , Narcolepsy/drug therapy , Sodium Oxybate/administration & dosage , Sodium Oxybate/toxicity , Substance Abuse, Oral/etiology , Substance Withdrawal Syndrome/drug therapyABSTRACT
A study was carried out on 50 workers in a floriculture centre to evaluate the incidence of contact dermatitis to Alstroemeria. 3 subjects gave positive reactions to aqueous and ethanolic extracts of cut flowers, stems and leaves. By column chromatography, the allergen was isolated and its chemical structure identified as 6-tuliposide A by proton magnetic resonance and carbon-13 magnetic resonance. Only 6-tuliposide A was isolated from cut flowers, and this gave positive reactions when patch tested at 0.01%; a-methylene-gamma-butyrolactone at 10(-5) (v/v) was positive in the same 3 subjects. Other lactones (gamma-methylene-gamma-butyrolactone, alantolactone, isoalantolactone) were negative at all concentrations used.