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

The 5-hydroxytryptamine receptor 2 (5-HT2) family is a subgroup of serotonin receptors belonging to the Class A G protein-coupled receptor (GPCR) superfamily [1.1.1, 1.3.1]. This family comprises three distinct subtypes: 5-HT2A, 5-HT2B, and 5-HT2C, which share significant structural homology and primarily signal through the Gq/11-phospholipase C pathway [1.1.3, 1.2.3]. These receptors are widely distributed throughout the central nervous system and peripheral tissues, where they regulate diverse physiological processes such as mood, cognition, perception, appetite, and vascular tone [1.1.5, 1.2.4]. Dysregulation of 5-HT2 receptor signaling is a hallmark of several neuropsychiatric conditions, most notably schizophrenia, major depressive disorder, and anxiety [1.2.1, 1.3.3]. As a result, the family represents a primary target for a broad range of pharmacological agents, including atypical antipsychotics, which often act as 5-HT2A/2C antagonists, and psychedelic compounds that function as 5-HT2A agonists [1.1.1, 1.1.4]. Therapeutic development within this family is complicated by "functional selectivity," where different ligands can bias signaling toward specific intracellular pathways [1.2.2, 1.2.4]. Furthermore, drug safety is a critical consideration, as off-target activation of 5-HT2B receptors has been linked to the development of cardiac valvulopathy [1.3.2]. Overall, the 5-HT2 receptor family remains a cornerstone of neuropharmacology and a key focus for treating complex mental health and metabolic disorders [1.2.1, 1.2.3].

Other names

5-hydroxytryptamine 2 receptor familySerotonin 2 receptor familyHTR2 family5-HT2R family

The 5-HT2 receptor family members (5-HT2A, 5-HT2B, and 5-HT2C) are Gq/11-coupled receptors that activate phospholipase C (PLC) [1.1.1, 1.1.2]. This activation leads to the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG) [1.2.2]. IP3 triggers the release of calcium from intracellular stores, while DAG activates protein kinase C (PKC) [1.2.2]. Additionally, these receptors exhibit functional selectivity (biased signaling), meaning different ligands can stabilize distinct receptor conformations that preferentially activate specific intracellular pathways, such as the arachidonic acid or beta-arrestin pathways, independent of the canonical Gq signaling [1.2.4, 1.3.2].