Serotonin receptor type 4 (5-HT4 receptor)

Serotonin receptor type 4 (5-HT4 receptor) is a G protein-coupled receptor (GPCR) expressed in the central and peripheral nervous systems, gastrointestinal tract, urinary bladder, heart, and adrenal gland [7][4][5]. It is encoded by the HTR4 gene and primarily couples to Gs proteins, stimulating the formation of cAMP upon activation by its endogenous ligand serotonin (5-hydroxytryptamine). The receptor is involved in neurotransmitter release modulation, gastrointestinal motility, and central functions such as mood and cognition. Clinically, selective 5-HT4 agonists are used to treat gastrointestinal disorders such as chronic idiopathic constipation and irritable bowel syndrome, and the receptor is under exploration as a therapeutic target for depression, cognitive impairment, and movement disorders [4][10]. Agents acting at the 5-HT4 receptor have shown promise for faster-onset antidepressant effects compared to classical therapies, but safety concerns—particularly cardiac risks—require careful pharmacological optimization of new drugs targeting this receptor [4][6].

Other names

5-hydroxytryptamine receptor 4HTR45-HT4R

Agonists stimulate the 5-HT4 receptor, resulting in increased production of cyclic AMP (cAMP) via Gs protein coupling, leading to enhanced neurotransmitter release and stimulation of gastrointestinal motility [3][4][5][7]. Some agents produce rapid antidepressant and anxiolytic effects by increasing cAMP in central nervous system pathways [4][10].