5-hydroxytryptamine receptor 1 family (5-HT1R) (5-HT1R)

The 5-HT1 receptor family comprises five G protein-coupled receptor subtypes (5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F) that primarily signal through the inhibition of adenylyl cyclase via Gi/o proteins (StatPearls, 2023). These receptors are widely distributed throughout the central and peripheral nervous systems and are involved in modulating neuronal excitability and neurotransmitter release (UniProt, 2024). 5-HT1A receptors are significant targets for treating anxiety and depression, acting as both presynaptic autoreceptors and postsynaptic receptors. 5-HT1B and 5-HT1D receptors are the primary targets for triptans used in acute migraine management, where they mediate cranial vasoconstriction and inhibit the release of calcitonin gene-related peptide (PubMed, 2022). The 5-HT1F receptor is a more recent target for migraine therapy (e.g., lasmiditan) that provides efficacy without the vasoconstrictive side effects associated with 5-HT1B activation (NIH, 2023). Collectively, these receptors play vital roles in regulating mood, pain processing, and vascular tone. Pharmacological modulation of these subtypes is a cornerstone of neuropsychiatric and neurovascular medicine. Safety concerns for drugs targeting this family include serotonin syndrome and potential cardiovascular risks for specific subtype agonists. Research continues into the specific roles of the less-understood 5-HT1E subtype. Overall, the 5-HT1 family represents a diverse and clinically essential group of therapeutic targets.

Other names

Serotonin 1 receptors5-HT1 receptor subtypes5-HT1 family

Agonism of 5-HT1 receptors typically activates Gi/o-coupled signaling pathways, leading to the inhibition of adenylyl cyclase, reduction of cAMP, and subsequent hyperpolarization of the neuron or inhibition of neurotransmitter release (IUPHAR/BPS, 2023).