5-hydroxytryptamine receptor 2 (5-HT2 receptor) (5-HT2R)

The 5-hydroxytryptamine receptor 2 (5-HT2 receptor) family is a group of G protein-coupled receptors (GPCRs) comprising three distinct subtypes: 5-HT2A, 5-HT2B, and 5-HT2C [1, 2]. These receptors primarily signal through the Gq/11 protein pathway, leading to the activation of phospholipase C and subsequent intracellular calcium mobilization [2, 3]. They are widely expressed in the central nervous system, where they modulate complex behaviors such as mood, cognition, perception, and appetite, as well as in peripheral tissues like vascular smooth muscle and platelets [3, 4]. The 5-HT2A subtype is a key target for atypical antipsychotics (antagonists) and psychedelic substances (agonists), while the 5-HT2C subtype is a significant target for metabolic regulation and obesity treatment [5, 6]. A critical safety consideration in drug development is the avoidance of 5-HT2B receptor agonism, which is strongly associated with the development of cardiac valvulopathy [7, 8]. Consequently, achieving high subtype selectivity is a primary goal for therapeutic agents targeting this family to treat conditions ranging from schizophrenia and depression to obesity and migraine [2, 9]. The family also plays a role in sleep-wake regulation and platelet aggregation, making it a versatile target in both neurology and cardiology [2, 3].

Other names

Serotonin 2 receptor5-HT2HTR25-hydroxytryptamine receptor family 2

Antagonism or inverse agonism of 5-HT2A for antipsychotic and antidepressant effects; Agonism of 5-HT2C for appetite suppression; Agonism of 5-HT2A for psychedelic-assisted therapy; Antagonism of 5-HT2B/2C for migraine prophylaxis.