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

The 5-hydroxytryptamine receptor 1B and 1D (5-HT1B/1D) are G protein-coupled receptors that serve as critical regulators of vascular tone and neurotransmitter release. Primarily located on cranial blood vessels and trigeminal nerve endings, these receptors are the principal targets for triptan medications used in the acute treatment of migraine and cluster headaches [1, 10]. Activation of the 5-HT1B subtype induces vasoconstriction of dilated meningeal vessels, while 5-HT1D activation inhibits the release of pro-inflammatory neuropeptides like calcitonin gene-related peptide (CGRP), thereby suppressing neurogenic inflammation and pain transmission [12, 15]. Beyond their role in headache, these receptors act as inhibitory autoreceptors and heteroreceptors in the central nervous system, influencing the release of serotonin, dopamine, and glutamate, which links them to the regulation of mood, anxiety, and impulsive behavior [2, 19]. Despite their therapeutic efficacy, the vasoconstrictive effects of 5-HT1B agonists present significant safety risks, particularly for patients with cardiovascular diseases such as coronary artery disease or uncontrolled hypertension [13, 20]. Consequently, clinical use requires careful patient screening to avoid adverse events like myocardial infarction or stroke [10, 22].

Other names

HTR1BHTR1DSerotonin 1D beta receptorSerotonin 1D alpha receptor5-HT1B5-HT1DS12Gpcr14

Agonists activate Gi/o-coupled 5-HT1B and 5-HT1D receptors, leading to the inhibition of adenylate cyclase and reduction of intracellular cAMP. This results in three primary therapeutic effects for migraine: vasoconstriction of dilated intracranial blood vessels (mediated by 5-HT1B), inhibition of pro-inflammatory neuropeptide release (such as CGRP and substance P) from trigeminal nerve terminals (mediated by 5-HT1D), and reduction of nociceptive transmission within the trigeminal nucleus caudalis [1, 12, 15].