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

The 5-hydroxytryptamine receptor 2 (5-HT2) family is a group of G protein-coupled receptors (GPCRs) that mediate many of the central and peripheral physiological functions of serotonin [StatPearls: Physiology, Serotonin, 2023]. This family comprises three subtypes: 5-HT2A, 5-HT2B, and 5-HT2C, which primarily signal through the Gq/11 pathway to activate phospholipase C and increase intracellular calcium levels [UniProt: P28223, P41595, P28335]. In the central nervous system, these receptors are critical for modulating mood, cognition, perception, and sleep [PubMed: 30925171]. In the periphery, they regulate vascular tone and platelet aggregation [PubMed: 30925171]. Dysregulation of 5-HT2 signaling is implicated in various psychiatric conditions, including schizophrenia, depression, and anxiety, as well as physiological disorders like obesity and migraine [NCBI Gene: 3356]. Pharmacologically, 5-HT2A antagonism is a hallmark of atypical antipsychotics, which help mitigate the side effects of dopamine D2 blockade while treating symptoms of psychosis [PubChem: CID 2722]. Conversely, 5-HT2C agonists have been developed for appetite suppression and weight management [PubMed: 24903070]. A significant challenge in targeting this family is achieving selectivity, as off-target activation of the 5-HT2B subtype is linked to the development of valvular heart disease [PubMed: 15131000]. Additionally, 5-HT2A receptors are the primary site of action for serotonergic psychedelics, which are currently being investigated for their therapeutic potential in treatment-resistant depression [PubMed: 32760105].

Other names

Serotonin 2 receptorHTR25-HT2 receptor family

Antagonism, inverse agonism, and agonism