5-hydroxytryptamine receptor 1 family (5-HT1) (5-HT1)

The 5-hydroxytryptamine receptor 1 (5-HT1) family is a group of G protein-coupled receptors (GPCRs) that respond to the neurotransmitter serotonin. This family includes five distinct subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F, all of which primarily signal through Gi/o proteins to inhibit adenylyl cyclase (StatPearls, 2023). These receptors are predominantly located in the central nervous system, where they act as both presynaptic autoreceptors and postsynaptic receptors to regulate neuronal excitability and the release of various neurotransmitters (UniProt, 2024). The 5-HT1 family plays a critical role in modulating mood, anxiety, sleep, and pain perception (PubMed, 2022). Pharmacologically, 5-HT1A receptors are key targets for anxiolytic and antidepressant drugs like buspirone and vilazodone (NIH, 2023). The 5-HT1B and 5-HT1D subtypes are the primary targets for triptans, which induce cranial vasoconstriction and inhibit pro-inflammatory neuropeptide release to treat acute migraines (PubChem, 2024). More recently, 5-HT1F receptor agonists, known as ditans, have been developed as migraine treatments that lack the vasoconstrictive side effects of triptans (PubMed, 2021). Dysregulation of 5-HT1 receptor signaling is associated with a wide range of conditions, including major depressive disorder, generalized anxiety disorder, and certain types of chronic pain (StatPearls, 2023).

Other names

5-HT1 receptorsSerotonin 1 receptors5-hydroxytryptamine 1 receptorsHTR1 family

Drugs targeting the 5-HT1 family primarily act as agonists that bind to the receptor's orthosteric site, triggering the activation of Gi/o-type G proteins (StatPearls, 2023). This activation inhibits adenylyl cyclase, leading to a decrease in intracellular cAMP concentrations, which subsequently modulates the activity of protein kinase A and ion channels, such as G protein-coupled inwardly rectifying potassium (GIRK) channels and voltage-gated calcium channels (UniProt, 2024). The resulting neuronal hyperpolarization and reduced neurotransmitter release underlie the therapeutic effects in anxiety, depression, and migraine (PubMed, 2022).