5-hydroxytryptamine receptor 2 family (5-HT2 receptor)

The 5-hydroxytryptamine receptor 2 (5-HT2) family is a group of G protein-coupled receptors (GPCRs) comprising three distinct subtypes: 5-HT2A, 5-HT2B, and 5-HT2C. These receptors are widely distributed throughout the central nervous system and peripheral tissues, where they modulate neuronal excitability, mood, perception, and smooth muscle tone [Source: UniProt]. The 5-HT2A receptor is a primary target for atypical antipsychotics and is the mediator of the effects of psychedelic substances like LSD [Source: PubMed]. 5-HT2C receptors are involved in the regulation of appetite and energy balance, serving as targets for weight management therapies [Source: NIH]. However, the 5-HT2B receptor is a significant safety liability; its activation is linked to drug-induced valvular heart disease, leading to the withdrawal of several medications from the market [Source: StatPearls]. Consequently, achieving subtype selectivity is a major challenge and goal in the development of drugs targeting this family to treat conditions ranging from schizophrenia to obesity. These receptors primarily signal through the Gq/11 pathway, leading to the activation of phospholipase C and subsequent increases in intracellular calcium [Source: IUPHAR/BPS Guide to Pharmacology].

Other names

Serotonin 2 receptors5-HT2 receptorsHTR2 family5-hydroxytryptamine 2 receptors

Drugs targeting the 5-HT2 receptor family act as agonists, antagonists, or inverse agonists to modulate Gq/11-mediated signaling. Activation of these receptors stimulates phospholipase C (PLC), which catalyzes the conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG), resulting in the release of intracellular calcium and activation of protein kinase C (PKC) [Source: IUPHAR/BPS Guide to Pharmacology].