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

The 5-hydroxytryptamine receptor 2A (5-HT2A) and 2B (5-HT2B) are subtypes of the G protein-coupled receptor (GPCR) superfamily that mediate the physiological effects of serotonin (UniProt P28223, P41595). 5-HT2A is predominantly expressed in the central nervous system, particularly in the cerebral cortex, where it modulates excitatory neurotransmission, mood, and perception (PubMed PMID: 10591247). It is a primary target for atypical antipsychotics, which typically act as antagonists to alleviate symptoms of schizophrenia, and for psychedelic compounds like psilocybin, which act as agonists. In contrast, 5-HT2B is found extensively in peripheral tissues, including the heart valves and gastrointestinal tract, where it regulates smooth muscle contraction and cardiac development (IUPHAR/BPS Guide to Pharmacology). While 5-HT2B has been explored as a target for migraine and IBS, it is most notable in drug development as a critical 'anti-target' because its chronic activation is strongly linked to drug-induced valvular heart disease and pulmonary hypertension (PubMed PMID: 11134430). Consequently, achieving high selectivity for 5-HT2A over 5-HT2B is a major safety requirement for new neuropsychiatric medications to avoid cardiotoxic side effects.

Other names

HTR2AHTR2BSerotonin 2A receptorSerotonin 2B receptor5-HT2A/2B5-hydroxytryptamine receptor 2A5-hydroxytryptamine receptor 2B

Antagonism or inverse agonism of 5-HT2A for antipsychotic and antidepressant effects; Agonism of 5-HT2A for psychedelic effects; Agonism of 5-HT2B associated with valvular fibroproliferation; Antagonism of 5-HT2B for migraine prophylaxis.