5-hydroxytryptamine receptor 1B (HTR1B) (HTR1B)

The 5-hydroxytryptamine receptor 1B (HTR1B) is a G protein-coupled receptor that mediates inhibitory neurotransmission by coupling to Gi/o proteins to decrease intracellular cAMP levels (UniProt: P28222). It functions as both a presynaptic autoreceptor, regulating serotonin release, and a heteroreceptor, modulating the release of other neurotransmitters such as GABA and glutamate (PubMed: 25839611). HTR1B is highly expressed in the basal ganglia, striatum, and on cranial blood vessels, where its activation leads to vasoconstriction (IUPHAR/BPS Guide to Pharmacology). This receptor is a primary therapeutic target for migraines, with triptan medications acting as selective agonists to alleviate symptoms by constricting dilated intracranial arteries and inhibiting trigeminal nerve activity (StatPearls: NBK554507). Beyond migraine, HTR1B is implicated in the pathophysiology of depression, anxiety, and impulsive behavior, including aggression and substance abuse (PubMed: 22101911). Therapeutic challenges include potential coronary vasoconstriction, which limits the use of HTR1B agonists in patients with cardiovascular disease (PubMed: 15554886). Ongoing research also explores HTR1B as a potential target for treating cognitive deficits and obsessive-compulsive disorder (PubMed: 15121188).

Other names

5-HT1B5-HT1DBHTR1D2S12Serotonin 1B receptor5-HT1D-beta

HTR1B agonists, such as triptans, bind to the receptor to activate Gi/o-mediated signaling, which inhibits adenylate cyclase and reduces cAMP production (UniProt: P28222). In migraine treatment, this activation leads to the contraction of smooth muscle in cranial blood vessels and the inhibition of pro-inflammatory neuropeptide release from trigeminal afferents (StatPearls: NBK554507). Conversely, HTR1B antagonism is being explored for antidepressant effects by increasing synaptic serotonin levels (PubMed: 25839611).