Serotonin 5-hydroxytryptamine receptor 1E (for 5-HT1E) and Serotonin 5-hydroxytryptamine receptor 1F (for 5-HT1F) (5-HT1E receptor (for 5-HT1E), 5-HT1F receptor (for 5-HT1F))

Serotonin 5-hydroxytryptamine receptor 1E and 1F (5-HT1E and 5-HT1F) are closely related members of the serotonin (5-HT) receptor family, specifically of the 5-HT1 class. Both are G protein-coupled receptors (GPCRs) that typically couple to Gαi/o proteins, mediating inhibition of the enzyme adenylate cyclase, thus reducing intracellular cAMP levels and modulating downstream signaling. They have high sequence homology to each other and to other 5-HT1 subtypes, but differ in tissue distribution and function. 5-HT1E is notably abundant in the hippocampus and cortex, where it may contribute to neuroprotective signaling and modulation of cell survival pathways, while 5-HT1F is implicated in migraine pathophysiology and is an established target for anti-migraine drugs like lasmiditan. Both receptors are considered potential therapeutic targets for neuropsychiatric and neurological conditions including depression, anxiety, neurodegenerative diseases, and migraine. Selectivity among receptor subtypes remains an important challenge for drug development due to shared structural features[7][4][3][1].

Other names

5-hydroxytryptamine receptor 1E (5-HT1E)HTR1E (gene)5-hydroxytryptamine receptor 1F (5-HT1F)HTR1F (gene)Serotonin receptor 1ESerotonin receptor 1F

Gαi/o-coupled inhibition of adenylate cyclase, reducing intracellular cAMP levels[7][4]; Modulation of ERK-BCL2 signaling pathways, sometimes leading to neuroprotection (for 5-HT1E)[4]; Agonist binding can trigger downstream pathways controlling neurotransmitter release, neuronal excitability, or neuroprotection[4][3]