Serotonin 5-hydroxytryptamine receptor 2A (5-HT2A receptor) (5-HT2A receptor (5-HT2AR))

The Serotonin 5-hydroxytryptamine receptor 2A (5-HT2A receptor) is a class A G protein-coupled receptor that serves as a primary excitatory serotonin receptor subtype and couples mainly to Gq/11 to activate phospholipase C and calcium-dependent intracellular signaling, with additional signaling via β-arrestin2 and, depending on ligand and context, Gi proteins[3][5][4]. It is the principal molecular target mediating the effects of serotonergic psychedelics and is a prominent therapeutic target in psychiatry, including schizophrenia and mood disorders; atypical antipsychotics often antagonize this receptor, and ligand bias at 5-HT2A can differentially influence cognition, psychosis-related behaviors, and psychedelic-like effects[3][4][1][5].

Other names

5-HT2AHTR2A (human gene symbol)Serotonin receptor 2A5-hydroxytryptamine receptor 2A

Agonists: activate 5-HT2A to engage Gq/11 signaling; Gq efficacy correlates with psychedelic-like effects in rodent head-twitch response. β-arrestin–biased agonists: recruit β-arrestin2, can lack psychedelic potential and may induce receptor downregulation/tachyphylaxis. Antagonists/inverse agonists (e.g., many atypical antipsychotics): block 5-HT2A-mediated pathways implicated in psychosis; broad pathway inhibition may reduce efficacy and cause side effects, motivating pathway-selective modulation. Context-dependent Gi coupling: certain ligands can drive Gαi1/Gαi3 signaling linked to specific behavioral outcomes.