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

The serotonin 5-HT1B and 5-HT1D receptors are closely related subtypes of G protein-coupled receptors that primarily function as inhibitory presynaptic receptors in the central nervous system and cerebral vasculature. Both receptors have a seven-transmembrane domain structure typical of GPCRs and couple to Gi/Go proteins, resulting in decreased intracellular cyclic AMP levels and inhibition of neurotransmitter release. Located on axon terminals of serotonergic (autoreceptors) and non-serotonergic neurons (heteroreceptors), they regulate the release of several neurotransmitters, such as serotonin, glutamate, GABA, noradrenaline, and acetylcholine, thus playing key roles in mood, aggression, addiction, memory, sleep, vascular tone, and migraine pathophysiology. Their activation in cranial blood vessels causes vasoconstriction, which underlies the therapeutic effect of "triptan" drugs in migraine, but also results in potential cardiovascular side effects. Variations in the genes encoding these receptors are associated with psychiatric and neurological disorders, and their pharmacological modulation is a target for antimigraine and potential neuropsychiatric therapies.

Other names

5-HT1B receptor5-HT1D receptorSerotonin receptor 1BSerotonin receptor 1DHTR1B (gene symbol)HTR1D (gene symbol)5-hydroxytryptamine 1B receptor5-hydroxytryptamine 1D receptor

Agonists (e.g., sumatriptan, ergotamine) act by stimulating 5-HT1B/1D receptors leading to vasoconstriction of cerebral and cranial blood vessels and inhibition of neuropeptide release, thus aborting migraine attacks. Antagonists/inverse agonists increase serotonin release by blocking inhibitory signals.