5-hydroxytryptamine receptor 1B (HTR1B) and 5-hydroxytryptamine receptor 1D (HTR1D) (5-HT1B and 5-HT1D)

5-hydroxytryptamine receptor 1B and 5-hydroxytryptamine receptor 1D are closely related G protein-coupled receptors that mediate the effects of serotonin (5-HT) in both the central nervous system and peripheral tissues. They are encoded by separate genes (HTR1B and HTR1D, respectively) and share significant sequence and pharmacological similarity. 5-HT1B is found in the brain and on vascular endothelium, where it functions in neurotransmitter regulation (inhibiting dopamine and serotonin release, modulating glutamate) and mediates vasoconstriction in cranial vessels—an effect especially relevant for migraine therapy. 5-HT1D is mainly expressed in the CNS (basal ganglia, raphe nuclei) and also participates in migraine and pain signaling. Both receptors are the primary targets of triptan drugs, which are first-line therapies for acute migraine due to their ability to constrict cerebral blood vessels and inhibit neuropeptide release. Drugs targeting these receptors must be used with caution in patients with cardiovascular risk due to the role in vasoconstriction.

Other names

Serotonin receptor 1BSerotonin receptor 1D5-HT-1B5-HT-1DHTR1BHTR1DS125-HT-1D-betaSerotonin 1D beta receptor5-hydroxytryptamine receptor 1D5-HT1B/1D receptor

Agonists (mainly triptans) activate 5-HT1B/1D receptors to induce cranial vasoconstriction and inhibit the release of vasoactive neuropeptides (e.g., CGRP, substance P) from trigeminal neurons, reducing migraine pain and neurogenic inflammation. Antagonists or inverse agonists can block serotonin action to modulate CNS excitability.