5-hydroxytryptamine receptor 1B and 5-hydroxytryptamine receptor 1D (5-HT1B/1D)

The 5-hydroxytryptamine receptor 1B and 1D (5-HT1B/1D) are subtypes of G protein-coupled receptors for serotonin that play a critical role in the pathophysiology and treatment of migraine and cluster headaches [1, 4]. These receptors are primarily located on intracranial blood vessels and trigeminal nerve endings, where their activation leads to vasoconstriction of painfully dilated cerebral arteries and the inhibition of pro-inflammatory neuropeptide release, such as calcitonin gene-related peptide (CGRP) [1, 3]. In the central nervous system, they function as both autoreceptors and heteroreceptors, modulating the release of serotonin and other neurotransmitters like dopamine and glutamate, which influences mood, anxiety, and nociceptive processing [6, 7, 8]. Drugs targeting these receptors, most notably the triptan class of agonists (e.g., sumatriptan), are the gold standard for acute migraine relief [1, 5]. However, because 5-HT1B receptors are also expressed in coronary arteries, their activation can cause off-target vasoconstriction, leading to significant cardiovascular safety concerns in patients with pre-existing heart disease [6, 16]. Beyond headache disorders, 5-HT1B/1D receptors are being investigated for their roles in obsessive-compulsive disorder, depression, and even certain cancers where they may regulate cell proliferation [11, 13, 18].

Other names

HTR1BHTR1D5-HT1B5-HT1D5-HT1D-beta5-HT1D-alphaSerotonin 1B receptorSerotonin 1D receptorS12RDC4

Agonism