γ-Hydroxybutyric Acid and Its Analogs, γ-Butyrolactone and 1,4-Butanediol

Abstract

Gamma-hydroxybutyric acid (GHB) is an endogenous compound in mammalian central nervous system and peripheral tissues and a minor metabolite or precursor of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter (Fig. 1). It was first synthesized in 1960 by Laborit (1) and his associates as an experimental GABA analog for possible use in the treatment of seizure disorder. They hypothesized that since GHB could readily cross the blood/brain barrier perhaps it could facilitate the synthesis of GABA in the brain. Although GHB did not produce elevated GABA synthesis, the research revealed that GHB had some pharmacologic properties that rendered it useful as an anesthetic adjuvant. The earliest pharmacological use of GHB in humans was in this application. Blumenfeld et al. (2) listed nine qualities observed from their experiments with GHB used in human anesthesia: mimics natural sleep, causes negligible reduction in minute respiratory volume, has cardiotonic effects, produces relaxation for ease of intubation, potentiates other central nervous system (CNS) depressants, does not change oxygen consumption, permits easy control of respiration, provides very stable vital signs, and permits slow induction of anesthesia. In this context Helrich et al. (3) correlated blood concentrations of GHB with state of consciousness in 16 adult human patients (Table 1).