Sites of Action of Gamma-Hydroxybutyrate (GHB)–A Neuroactive Drug with Abuse Potential

Abstract

When administered in pharmacological doses, its powerful central nervous system depressant effects are readily observed. Although some of the neurophysiological actions of GHB could involve alterations in dopaminergic transmission in the basal ganglia, both its physiological and pharmacological actions are probably mediated through specific brain receptors for GHB. In addition, GHB might mediate some of its effects through interaction with the GABA(B) receptor. Experimentally, GHB has been used as a model for petit mal epilepsy; clinically, it has been used as a general anesthetic and as a drug to treat certain sleep disorders and related conditions. Owing to the purported ability of GHB to induce a state of euphoria, recreational use of this substance is popular. Although no deaths or long-term problems have been associated with GHB abuse, symptoms of GHB intoxication can be severe. The continued potential for GHB abuse makes it imperative for clinical toxicologists to be aware of the effects of this agent. Future research on the mechanism of action of GHB is needed to elucidate both its central nervous system depressant properties and its ability to effect a state of well-being.

Prevalence of γ-hydroxybutyrate (GHB) in serum samples of amphetamine, metamphetamine and ecstasy impaired drivers

“…In the 1990s it emerged as a club drug (liquid ecstasy) due to its CNS depressive effects resulting from interaction with specific brain receptors for GHB and a possible interaction with the GABAb receptor [2]. Other effectsespecially at higher doses -can be confusion, dizziness, drowsiness, vomiting, amnesia, respiratory depression and even death [3].…”

Functional Modification of Proteins of the Nervous System by Pyridoxal 5′-Phosphate

“…Further, it has its own transport system and receptor site [74,75], although there is considerable evidence [76] that it can activate GABA B receptors also. In mouse brain PLP has an unusual effect on the Á-hydroxybutyrate transporter.…”

The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance: A Review

“…It was later discovered that GHB is an endogenous compound existing in the brain of humans [24]. EnGHB concentrations in the human brain reach about 11-25 μ M in the striatum [25], whereas the cerebellum and certain areas of the cerebral cortex contain the lowest concentrations [26]. ExGHB adds to these concentrations where GHB levels above the vitreous cut-off endogenous urine concentrations of 6-10 mg/l are considered to be exogenous [27,28].…”