Résumé
GABAB receptors are activated by γ-aminobutyric acid (GABA), an amino acid that serves as the primary inhibitory neurotransmitter in the central nervous system, with links to a range of neurological diseases. This receptor represents a promising drug target in the field of neurological diseases for the treatment of spasticity, alcohol use disorder, anxiety, and insomnia using therapeutic options such as baclofen and phenibut. The GABAB receptor belongs to class C of the G protein-coupled receptors and acts as an obligate heterodimer made up of two subunits, GABAB1 and GABAB2. Each subunit is comprised of an extracellular domain in which GABA and the above-mentioned therapeutic drugs bind and a transmembrane domain responsible for G protein activation. GABAB features a unique allosteric mechanism for signal transduction in which agonist binding in the GABAB1 extracellular domain elicits G protein activation via rearrangement of the intracellular face of the GABAB2 transmembrane domain. More recently, the GABAB receptor has been found to display a tendency to form oligomers, thus increasing the complexity of allosteric communications in the receptor. This chapter summarizes the current state-of-the-art relating to the structure, activation mechanism, and allosteric modulation of the GABAB receptor, which may provide novel opportunities for the development of approaches aimed at regulating receptor activity.