Dopamine D2 receptor and Serotonin 5-HT2A receptor (D2 receptor and 5-HT2A receptor)

The Dopamine D2 receptor and Serotonin 5-HT2A receptor are high-affinity, class A G protein-coupled receptors (GPCRs) that are central to the pharmacology of antipsychotic drugs and implicated in the pathophysiology of schizophrenia and other neuropsychiatric disorders. The D2 receptor primarily couples to Gi/o proteins and modulates dopaminergic neurotransmission, while the 5-HT2A receptor couples to Gq/11 and is involved in serotonergic signaling. These receptors are widely expressed in the central nervous system, especially in the prefrontal cortex, and functionally interact through heteromerization and signaling crosstalk, playing key roles in cognition, memory, and behavioral regulation. Blockade or modulation of both receptors is the core mechanism of action for many typical and atypical antipsychotics, with variations in receptor affinity influencing therapeutic efficacy and side-effect profiles. The 5-HT2A receptor is also the principal target of classic hallucinogens such as LSD and psilocin, whose agonism increases cortical glutamate and dopamine, contributing to hallucinogenic and psychotomimetic effects. Both DRD2 and HTR2A gene polymorphisms can influence symptom profiles and treatment responses in psychiatric disorders.

Other names

D2 receptorDRD2 (for Dopamine D2 receptor)5-HT2A receptorHTR2A (for Serotonin 5-HT2A receptor)Dopamine D2Serotonin 2A receptor

Antagonism/inverse agonism at D2 and/or 5-HT2A receptor (e.g., atypical antipsychotics); Blockade of D2 receptor-mediated dopaminergic signaling; Blockade of 5-HT2A receptor-mediated serotonergic signaling; Functional crosstalk and heteromerization: drugs may act on both receptors and heteromers, modifying efficacy and side effect profile