5-hydroxytryptamine receptor 2A and 5-hydroxytryptamine receptor 2C (5-HT2A and 5-HT2C)

5-hydroxytryptamine receptor 2A and 5-hydroxytryptamine receptor 2C Overview

5-hydroxytryptamine receptor 2A (5-HT2A) and 2C (5-HT2C) are closely related G protein-coupled receptors in the serotonin (5-HT) receptor family, primarily coupling to the Gq/11 signaling pathway. 5-HT2A is highly expressed in the brain cortex, modulating cognition, perception, and mood, and plays a major role in the mechanism of action of hallucinogens and atypical antipsychotic drugs. It is also involved in vascular tone regulation and platelet aggregation. 5-HT2C is predominantly found in the central nervous system (especially the hypothalamus and limbic structures) and regulates appetite, feeding behavior, and mood. Both receptors are promising therapeutic targets in psychiatric, metabolic, and neurologic disorders due to their differential roles in neurotransmission and disease. 5-HT2A receptor agonists include classical hallucinogens (LSD, psilocybin), while antagonists form an important component of atypical antipsychotics. 5-HT2C receptor agonists like lorcaserin are used for obesity, and various psychotropics influence this receptor as part of their mechanism. Both receptors are subject to regulated desensitization and internalization, with unique pharmacological regulatory properties compared to other GPCRs.

Mechanism of Action

Agonism (direct activation, as with hallucinogens for 5-HT2A, or appetite suppression for 5-HT2C) and antagonism or inverse agonism (blockade, as with antipsychotic and some antidepressant drugs targeting 5-HT2A) are key mechanisms. Functional selectivity, where some ligands preferentially activate or block specific downstream pathways, also plays a role.

Biological Functions

Safety Considerations

Interacting Drugs

Associated Biomarkers