STUDY OBJECTIVES: Gamma-hydroxybutyrate (GHB) was originally introduced as an anesthetic but was first abused by bodybuilders and then became a recreational or club drug.1 Sodium salt of GHB is currently used for the treatment of cataplexy in patients with narcolepsy. The mode of action and metabolism of GHB is not well understood. GHB stimulates growth hormone release in humans and induces weight loss in treated patients, suggesting an unexplored metabolic effect. In different experiments the effect of GHB administration on central (cerebral cortex) and peripheral (liver) biochemical processes involved in the metabolism of the drug, as well as the effects of the drug on metabolism, were evaluated in mice. DESIGN: C57BL/6J, gamma-aminobutyric acid B (GABAB) knockout and obese (ob/ob) mice were acutely or chronically treated with GHB at 300 mg/kg. MEASUREMENTS AND RESULTS: Respiratory ratio decreased under GHB treatment, independent of food intake, suggesting a shift in energy substrate from carbohydrates to lipids. GHB-treated C57BL/6J and GABAB null mice but not ob/ob mice gained less weight than matched controls. GHB dramatically increased the corticosterone level but did not affect growth hormone or prolactin. Metabolome profiling showed that an acute high dose of GHB did not increase the brain GABA level. In the brain and the liver, GHB was metabolized into succinic semialdehyde by hydroxyacid-oxoacid transhydrogenase. Chronic administration decreased glutamate, s-adenosylhomocysteine, and oxidized gluthathione, and increased omega-3 fatty acids. CONCLUSIONS: Our findings indicate large central and peripheral metabolic changes induced by GHB with important relevance to its therapeutic use.
STUDY OBJECTIVES:Gamma-hydroxybutyrate (GHB) was originally introduced as an anesthetic but was first abused by bodybuilders and then became a recreational or club drug.1 Sodium salt of GHB is currently used for the treatment of cataplexy in patients with narcolepsy. The mode of action and metabolism of GHB is not well understood. GHB stimulates growth hormone release in humans and induces weight loss in treated patients, suggesting an unexplored metabolic effect. In different experiments the effect of GHB administration on central (cerebral cortex) and peripheral (liver) biochemical processes involved in the metabolism of the drug, as well as the effects of the drug on metabolism, were evaluated in mice. DESIGN: C57BL/6J, gamma-aminobutyric acid B (GABAB) knockout and obese (ob/ob) mice were acutely or chronically treated with GHB at 300 mg/kg. MEASUREMENTS AND RESULTS: Respiratory ratio decreased under GHB treatment, independent of food intake, suggesting a shift in energy substrate from carbohydrates to lipids. GHB-treated C57BL/6J and GABAB null mice but not ob/ob mice gained less weight than matched controls. GHB dramatically increased the corticosterone level but did not affect growth hormone or prolactin. Metabolome profiling showed that an acute high dose of GHB did not increase the brain GABA level. In the brain and the liver, GHB was metabolized into succinic semialdehyde by hydroxyacid-oxoacid transhydrogenase. Chronic administration decreased glutamate, s-adenosylhomocysteine, and oxidized gluthathione, and increased omega-3 fatty acids. CONCLUSIONS: Our findings indicate large central and peripheral metabolic changes induced by GHB with important relevance to its therapeutic use.
Authors: G Gerra; R Caccavari; B Fontanesi; G Fertonani Affini; D Maestri; P Avanzini; A Zaimovic; D Franchini; R Delsignore Journal: Int Clin Psychopharmacol Date: 1995-11 Impact factor: 1.659
Authors: E Van Cauter; L Plat; M B Scharf; R Leproult; S Cespedes; M L'Hermite-Balériaux; G Copinschi Journal: J Clin Invest Date: 1997-08-01 Impact factor: 14.808
Authors: G Gerra; R Caccavari; B Fontanesi; A Marcato; G Fertonani Affini; D Maestri; P Avanzini; R Lecchini; R Delsignore; A Mutti Journal: Int Clin Psychopharmacol Date: 1994-09 Impact factor: 1.659
Authors: Claire E H M Donjacour; N Ahmad Aziz; Sebastiaan Overeem; Andries Kalsbeek; Hanno Pijl; Gert Jan Lammers Journal: Sleep Date: 2014-04-01 Impact factor: 5.849
Authors: Tingting Wang; Kirstine L Nielsen; Kim Frisch; Johan K Lassen; Camilla B Nielsen; Charlotte U Andersen; Palle Villesen; Mette F Andreasen; Jørgen B Hasselstrøm; Mogens Johannsen Journal: Front Pharmacol Date: 2022-03-03 Impact factor: 5.810
Authors: Roberto Arriga; Francesca Pacifici; Barbara Capuani; Andrea Coppola; Augusto Orlandi; Maria Giovanna Scioli; Donatella Pastore; Aikaterini Andreadi; Paolo Sbraccia; Manfredi Tesauro; Nicola Di Daniele; Giuseppe Sconocchia; Giulia Donadel; Alfonso Bellia; David Della-Morte; Davide Lauro Journal: Oxid Med Cell Longev Date: 2019-12-19 Impact factor: 6.543
Authors: Andrea E Steuer; Justine Raeber; Fabio Simbuerger; Dario A Dornbierer; Oliver G Bosch; Boris B Quednow; Erich Seifritz; Thomas Kraemer Journal: Metabolites Date: 2021-03-12