Gamma-hydroxybutyrate receptors (GHBR)

Gamma-hydroxybutyrate (GHB) receptors comprise two distinct populations of binding sites in the central nervous system: high-affinity GHB-specific receptors and low-affinity GABA-B receptors. The high-affinity GHB receptor is primarily excitatory and is currently understood to be either a unique G protein-coupled receptor or a specific subtype of the GABA-A receptor containing alpha4, beta, and delta subunits (Absalom et al., 2012). In contrast, the low-affinity site is the GABA-B receptor, where GHB acts as a weak agonist to produce its characteristic sedative, hypnotic, and anesthetic effects (Kaupmann et al., 2003). These receptors are widely distributed in brain regions such as the hippocampus, cortex, and basal ganglia, where they modulate the release of neurotransmitters including dopamine, glutamate, and GABA (Maitre et al., 2000). Clinically, the GHB receptor system is the primary target for sodium oxybate, which is FDA-approved for the treatment of cataplexy and excessive daytime sleepiness in patients with narcolepsy (StatPearls, 2023). Because GHB has a narrow therapeutic window and acts on the GABA-B receptor at higher concentrations, it carries significant risks of respiratory depression, coma, and abuse (Bay et al., 2014).

Other names

High-affinity GHB receptorLow-affinity GHB receptorGABA-B receptorGHB receptorGamma-hydroxybutyric acid receptor

Agonism of high-affinity GHB receptors (potentially alpha4beta1delta GABA-A subtypes) and low-affinity GABA-B receptors to modulate neuronal firing and inhibitory signaling.