5-hydroxytryptamine 1 and 5-hydroxytryptamine 2 receptors (5-HT1 and 5-HT2 receptors)

The 5-hydroxytryptamine 1 (5-HT1) and 5-hydroxytryptamine 2 (5-HT2) receptors are families of serotonin (5-HT) receptors expressed throughout the central and peripheral nervous system, as well as in other tissues. Both are G protein-coupled receptors comprising multiple subtypes with unique anatomical distributions, pharmacology, and functional roles. 5-HT1 receptors generally mediate inhibitory effects through coupling to Gi/Go proteins, leading to decreased cAMP levels and increased potassium conductance—important in regulating mood, anxiety, pain perception, and serving as targets for antimigraine and antidepressant drugs. 5-HT2 receptors are typically excitatory, coupled to Gq proteins, and are implicated in modulating cognition, perception, vascular tone, and platelet aggregation. Subtype-selective agonists and antagonists target disorders such as depression, schizophrenia, migraine, and obesity. Atypical antipsychotics commonly act as 5-HT2A antagonists and functional 5-HT1A agonists. Therapeutic use is restricted by side effects such as hallucinations, heart valve dysfunction, and the need for high subtype selectivity. The two families are central to the pharmacology of many widely used CNS drugs, and their diverse functions make them highly relevant therapeutic targets—although precise targeting of subtypes is necessary for safe and effective treatment.

Other names

Serotonin 1 receptorSerotonin 2 receptor5-HT1 family5-HT2 family5-HT1A5-HT1B5-HT1D5-HT2A5-HT2B5-HT2C

Agonism or antagonism of GPCR-mediated signaling. 5-HT1: Typically inhibits adenylyl cyclase, opens K+ channels (hyperpolarization, inhibition). 5-HT2: Typically activates phosphoinositide hydrolysis, PKC, increases neuronal excitability. Modulation of neurotransmitter release (serotonin, dopamine, acetylcholine).