Serotonin receptor 2A and Serotonin receptor 2B (5-HT2A and 5-HT2B receptor)

The serotonin receptor 2A (5-HT2A) and serotonin receptor 2B (5-HT2B) are closely related members of the serotonin (5-hydroxytryptamine, 5-HT) receptor family, both classified as G protein-coupled receptors (GPCRs). These receptors share significant structural homology, especially in their transmembrane domains. 5-HT2A receptors are predominantly found in the central nervous system and regulate important brain processes including mood, cognition, and perception; they are notably the primary target for many psychedelic compounds, which exert their effects by activating and producing functionally selective signaling through these receptors. 5-HT2B receptors are mainly expressed in peripheral tissues such as cardiac muscle and vasculature, where they regulate cardiovascular functions; activation of 5-HT2B can lead to adverse effects such as drug-induced valvular heart disease, which is of critical importance for drug safety. Therapeutic drugs and research tools selectively modulate these receptors, with antagonists used in neuropsychiatric disorders and careful avoidance of 5-HT2B agonism in cardiovascular drug development. Both receptors exhibit complex signaling properties, including biased agonism, where different ligands can preferentially activate distinct intracellular pathways, contributing to their varied physiological and pathophysiological roles.

Other names

5-hydroxytryptamine receptor 2A5-hydroxytryptamine receptor 2B5-HT2A5-HT2BSerotonin 2A receptorSerotonin 2B receptor5-HT2A-R5-HT2B-R

Agonists: Activate Gq/11 protein signaling (phospholipase C activation, IP3/DAG pathway) Biased agonism: Recruit β-arrestin-2 pathway Antagonists: Block receptor activity, inhibiting downstream signaling (used in antipsychotic drugs and cardiovascular drug safety) Hallucinogens: Functional selectivity, produce biased signaling resulting in altered perception and cognition Drugs targeting 5-HT2B may cause cardiac valvulopathy