5-hydroxytryptamine receptor 2A (HTR2A) (HTR2A)

The 5-hydroxytryptamine receptor 2A (HTR2A) is a major G protein-coupled receptor (GPCR) in the serotonin receptor family, primarily signaling through the Gq/11-phospholipase C (PLC) pathway. It is extensively distributed throughout the central nervous system, with high density in the prefrontal cortex, where it regulates neuronal excitability, cognition, and perception. HTR2A is a primary target for atypical antipsychotics, such as clozapine, which function as antagonists or inverse agonists to treat schizophrenia and related psychotic disorders. Additionally, the receptor is the principal site of action for serotonergic psychedelics like LSD and psilocybin, which act as agonists to produce hallucinogenic effects. Beyond its neurological roles, HTR2A is involved in peripheral functions including platelet aggregation and vasoconstriction. Genetic variations in the HTR2A gene, such as the rs6311 polymorphism, have been associated with susceptibility to various psychiatric conditions and differences in drug response.

Other names

5-HT2A receptorSerotonin receptor 2AHTR25-HT2S2 receptor

Drugs targeting HTR2A primarily act through antagonism or inverse agonism (e.g., atypical antipsychotics) to reduce serotonergic signaling, or through agonism (e.g., psychedelics) to enhance it. Some drugs also exhibit functional selectivity, differentially activating G protein-dependent or independent pathways such as Akt signaling.