5-hydroxytryptamine receptor 1 family (5-HT1)

The 5-hydroxytryptamine receptor 1 (5-HT1) family consists of five distinct G protein-coupled receptor subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F (IUPHAR/BPS Guide to Pharmacology). These receptors are primarily coupled to Gi/o proteins, which inhibit the enzyme adenylyl cyclase and reduce the production of cyclic adenosine monophosphate (cAMP) within the cell (UniProt). They play a critical role in the central and peripheral nervous systems, regulating neurotransmitter release, mood, cognition, and vascular tone (PubMed, PMID: 11519307). Clinically, the 5-HT1 family is a major therapeutic target for several conditions; for instance, 5-HT1A receptors are targeted for anxiety and depression, while 5-HT1B and 5-HT1D receptors are the primary targets for triptans used in the acute treatment of migraines (StatPearls). Additionally, the 5-HT1F receptor has emerged as a target for non-vasoconstrictive migraine therapies like lasmiditan (NIH). Modulating these receptors allows for the fine-tuning of serotonergic signaling, though it requires careful management to avoid adverse effects like serotonin syndrome or excessive vasoconstriction (PubChem).

Other names

Serotonin 1 receptors5-HT1 receptors5-hydroxytryptamine 1 receptors5-HT1 receptor family

Drugs targeting the 5-HT1 receptor family primarily act as agonists or partial agonists to activate Gi/o protein-coupled pathways, leading to the inhibition of adenylyl cyclase and a decrease in intracellular cAMP levels (UniProt). In the context of migraines, 5-HT1B/1D agonists induce cranial vasoconstriction and inhibit the release of pro-inflammatory neuropeptides, while 5-HT1A agonists modulate neuronal firing in the central nervous system to alleviate anxiety and depression (StatPearls).