Serotonin 5-HT2A receptor, Serotonin 5-HT2B receptor, and Serotonin 5-HT2C receptor (5-HT2A, 5-HT2B, 5-HT2C)

The serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors are **closely related G protein-coupled receptors** within the serotonin receptor family, encoded by distinct genes (HTR2A, HTR2B, HTR2C). They share substantial sequence homology and structural features—most notably a **seven-transmembrane domain architecture**—but have distinctly different tissue distributions and physiological roles. - 5-HT2A receptors are highly expressed in the cortex and are critical to the mechanism of action of many hallucinogenic drugs (e.g., LSD, psilocin), as well as being targets for antipsychotics. They modulate perception, cognition, and mood, and participate in regulating neurotransmitter systems including dopamine and glutamate[1][3]. - 5-HT2B receptors are present in peripheral tissues such as the heart and gastrointestinal tract, where they play roles in cardiovascular homeostasis but are notorious for being implicated in drug-induced cardiac valvulopathy[5]. - 5-HT2C receptors are mainly expressed in the CNS (notably choroid plexus and limbic regions) and modulate mood, appetite, and neuroendocrine functions. They are targets for weight-loss drugs and certain antipsychotics and antidepressants[2][4]. All three receptor subtypes couple primarily to **Gq/11 proteins** that activate phospholipase C, increasing intracellular calcium and activating protein kinase C-mediated pathways[3]. Pharmacologically, they are targeted by various ligands acting as agonists, antagonists, or inverse agonists—many of which are of major clinical, pharmacological, or forensic interest. Dysfunction or misregulation of these receptors is implicated in psychiatric diseases, cardiovascular pathology, and adverse drug reactions[1][3][5].

Other names

5-HT2A receptor5-HT2B receptor5-HT2C receptorSerotonin receptor 2A, 2B, 2CHTR2A, HTR2B, HTR2C5-hydroxytryptamine receptor 2A, 2B, 2C

Agonists (e.g., LSD, psilocin) activate the receptor, triggering Gq/11-coupled signaling leading to phospholipase C (PLC) activation, increase in intracellular calcium, and downstream signaling pathways. Antagonists (e.g., M100907, ritanserin) block receptor activation and its downstream effects, often used to counteract psychotic symptoms or mitigate drug-induced effects. Inverse agonists (e.g., ritanserin) stabilize the inactive receptor conformation, reducing basal activity. The effect of individual ligands may differ between subtypes (e.g., certain drugs act as antagonists at 5-HT2A but agonists at 5-HT2C).