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

The 5-hydroxytryptamine receptor 1 (5-HT1) family is a group of G protein-coupled receptors (GPCRs) that play a critical role in modulating the central and peripheral nervous systems (StatPearls, 2023). 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 adenylate cyclase activity (UniProt, 2024). These receptors function as both inhibitory postsynaptic receptors and presynaptic autoreceptors, regulating the release of serotonin and other neurotransmitters like glutamate and GABA (PubMed, 2022). Clinically, 5-HT1 receptors are major therapeutic targets; for instance, 5-HT1A agonists are used to treat anxiety and depression, while 5-HT1B/1D agonists, known as triptans, are standard treatments for acute migraine (NIH, 2023). The 5-HT1F receptor has also emerged as a target for non-vasoconstrictive migraine therapies, such as lasmiditan (PubChem, 2024). Dysregulation of these receptors is linked to various psychiatric and neurological disorders, including major depressive disorder and chronic pain (Wikipedia, 2024). Pharmacological intervention must be carefully monitored to prevent serotonin syndrome, a condition of excessive serotonergic signaling that can be fatal (StatPearls, 2023).

Other names

Serotonin 1 receptor5-HT1 receptor family5-hydroxytryptamine 1 receptor

The primary mechanism of action for drugs targeting 5-HT1 receptors involves agonism or partial agonism, which activates Gi/o-coupled signaling pathways. This activation inhibits adenylate cyclase, leading to reduced intracellular cAMP levels, the opening of potassium channels, and the closing of voltage-gated calcium channels, ultimately resulting in neuronal hyperpolarization and the inhibition of neurotransmitter release (StatPearls, 2023; UniProt, 2024).