Multi-faceted aspects of gamma-hydroxybutyric acid: a neurotransmitter, therapeutic agent and drug of abuse.
Gamma hydroxybutyric acid (GHB), an endogenous constituent of the mammalian brain, acts as i) a neurotransmitter or neuromodulator, ii) a medicine used for the treatment of narcolepsy and alcoholism, and iii) a drug illicitly used for its psychotropic effects. GHB is thought to act as a specific GHB receptor agonist as well as a weak gamma-aminobutyric acid type B (GABA(B)) receptor agonist. Here, I review the in vivo and in vitro pharmacological properties of GHB and its interaction with GHB and GABA(B) receptors. When exogenously administered, GHB is rapidly absorbed, crosses the blood-brain barrier, penetrates into the brain and exerts a number of pharmacological effects including anxiolysis, sedation/hypnosis and anesthesia. Due to its effects on the central nervous system, GHB has been used for the treatment of narcolepsy and as an anesthetic adjuvant. More recently, a role for GHB in the pharmacotherapy of alcohol dependence has been described. In this review, I also focus on the abuse liability and reinforcing properties of GHB in humans and laboratory animals.
B. B. Brodie Department of Neuroscience, University of Cagliari, Cagliari, Italy. castelli@unica.it
M Paola
MP
Castelli
D000437:Alcoholism; D000758:Anesthesia; D000818:Animals; D001665:Binding Sites; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D004594:Electrophysiology; D000882:Haplorhini; D006801:Humans; D006885:Hydroxybutyrates / Q000737:chemistry*; D006990:Hypnosis; D008024:Ligands; D008956:Models, Chemical; D018377:Neurotransmitter Agents / Q000737:chemistry*; D015398:Signal Transduction
D006885:Hydroxybutyrates; D008024:Ligands; D018377:Neurotransmitter Agents; C111420:4-hydroxybutyric acid