5HT1F

5HT1F, or the serotonin 1F receptor, is a member of the 5-HT1 family of G protein-coupled receptors. It is a seven-transmembrane receptor that preferentially couples to Gi/o proteins, leading to inhibition of adenylyl cyclase and a fall in intracellular cAMP. Activation can influence ion channels and neuronal excitability, contributing to modulation of neurotransmitter release in brain circuits.

In humans, 5-HT1F receptors are expressed in the central nervous system, with notable levels in the trigeminal ganglia, brainstem, and various cortical regions. In the trigeminovascular system, 5-HT1F receptors are thought to constrain the release of pro-nociceptive mediators such as CGRP, supporting a role in the modulation of migraine pathways without directly driving vascular constriction.

Endogenous serotonin is the natural ligand for 5-HT1F. The receptor has become a pharmacological target for acute treatment of migraine. Selective 5-HT1F receptor agonists, known as ditans, include lasmiditan, which is approved for acute migraine management. Compared with triptans, 5-HT1F agonists are associated with little or no vasoconstriction, which can be advantageous for patients with cardiovascular risks.

Clinical use and research status: lasmiditan has demonstrated efficacy in clinical trials and is indicated for acute treatment of migraine with or without aura. Common adverse effects include dizziness, fatigue, and somnolence. Ongoing research investigates additional ligands and potential roles in other CNS conditions, but migraine therapy remains the primary approved indication as of now.