Gamma-aminobutyric acid type B receptor (GABA-B receptor) (GABABR)

The Gamma-aminobutyric acid type B (GABA-B) receptor is a metabotropic G protein-coupled receptor (GPCR) that mediates slow, prolonged inhibitory neurotransmission in the central nervous system (UniProt, 2024). It functions as a mandatory heterodimer composed of GABBR1 and GABBR2 subunits, which are primarily coupled to Gi/o-type G proteins (Bettler et al., 2004). Activation of the receptor leads to the inhibition of adenylyl cyclase, the opening of G protein-coupled inwardly rectifying potassium (GIRK) channels, and the inhibition of voltage-gated calcium channels, resulting in neuronal hyperpolarization and reduced neurotransmitter release (StatPearls, 2023). Clinically, the GABA-B receptor is the primary target for baclofen, a drug used to treat spasticity associated with multiple sclerosis and spinal cord injuries (StatPearls, 2023). The phrase "via conversion to baclofen" refers to prodrugs like arbaclofen placarbil, which are metabolized into the active agonist to improve absorption and systemic exposure (NCBI, 2012). Beyond motor control, the receptor is implicated in alcohol use disorder, chronic pain, and anxiety, making it a significant focus for neuropsychiatric drug development (Enna and Bowery, 2004). Safety concerns associated with GABA-B modulation include profound sedation, dizziness, and a potentially severe withdrawal syndrome if the drug is discontinued abruptly (StatPearls, 2023).

Other names

GABA-B receptorGABAB receptorMetabotropic GABA receptorG-protein coupled GABA receptorGABBR1/GABBR2 heterodimerGABBR

Agonism of the GABA-B receptor activates Gi/o proteins, which inhibits adenylyl cyclase, opens G protein-coupled inwardly rectifying potassium (GIRK) channels, and closes voltage-gated calcium channels, leading to pre- and post-synaptic inhibition (StatPearls, 2023; UniProt, 2024).