# 5-HT1B receptor

5-hydroxytryptamine receptor 1B also known as the 5-HT$_{1B}$ receptor is a protein that in humans is encoded by the HTR1B gene. The 5-HT$_{1B}$ receptor is a 5-HT receptor subtype.

## Tissue distribution and function

5-HT$_{1B}$ receptors are widely distributed throughout the central nervous system with the highest concentrations found in the frontal cortex, basal ganglia, striatum, and the hippocampus. The function of the 5-HT$_{1B}$ receptor differs depending upon its location. In the frontal cortex, it is believed to act as a terminal receptor inhibiting the release of dopamine. In the basal ganglia and the striatum, evidence suggests 5-HT signaling acts on an autoreceptor, inhibiting the release of serotonin and decreasing glutamatergic transmission by reducing miniature excitatory postsynaptic potential (mEPSP) frequency, respectively. In the hippocampus, a recent study has demonstrated that activation of postsynaptic 5-HT$_{1B}$ heteroreceptors produces a facilitation in excitatory synaptic transmission which is altered in depression. When the expression of 5-HT$_{1B}$ in human cortex was traced throughout life, significant changes during adolescence were observed, in a way that is strongly correlated with the expression of 5-HT$_{1E}$.
Outside of the CNS, the 5-HT$_{1B}$ receptor is also expressed on the endothelium of blood vessels, particularly in the meninges. Activation of these receptors results in vasoconstriction. The high distribution of vasoconstrictive 5-HT$_{1B}$ and 5-HT$_{1D}$ receptors around the brain makes them a valuable drug target for the treatment of migraines.
Blocking 5-HT$_{1B}$ receptor signalling also increases the number of osteoblasts, bone mass, and the bone formation rate.
Knockout mice lacking the 5-HT$_{1B}$ gene have been reported to have a higher preference for alcohol, although later studies failed to replicate such abnormalities in alcohol consumption. These mice have also been reported to have a lower measure of anxiety (such as on the elevated plus maze test) and a higher measure of aggression.
Under basal conditions, knockout mice present with a "normal" phenotype and exhibit a sucrose preference (lack of sucrose preference is considered a measure of anhedonia). However, after undergoing chronic unpredictable stress treatment to induce a "depression-like" phenotype these animals do not benefit from administration of selective serotonin reuptake inhibitor (SSRIs).
Activation of the serotonin 5-HT$_{1B}$ receptor appears to mediate the prosocial effects of entactogens acting as serotonin releasing agents like MDMA in animals. In addition, serotonin 5-HT$_{1B}$ receptor activation appears to mediate the locomotor hyperactivity of these agents. The serotonin 5-HT$_{1B}$ receptor also appears to be required for the persisting antidepressant- and anxiolytic-like effects as well as acute hypolocomotion of the serotonergic psychedelic and non-selective serotonin receptor agonist psilocybin in animals.

## Ligands
### Agonists

* 2ZEDMA (also a 5-HT$_{2A}$ agonist)
* 5-Carboxamidotryptamine (5-CT)
* Almotriptan
* Anpirtoline (D-16949)
* Avitriptan
* Batoprazine
* CGS-12066A
* CP-93,129 (peripherally acting)
* CP-94,253
* CP-122,288 (mixed 5-HT$_{1B/1D}$ agonist)
* CP-135,807 (mixed 5-HT$_{1B/1D}$ agonist)
* Dihydroergotamine
* Donitriptan
* Eletriptan
* Eltoprazine (DU-28853)
* Ergotamine
* Fluprazine
* Frovatriptan
* L-741,604
* Lisuride
* mCPP
* Methylergometrine (methylergonovine)
* Methysergide
* Naratriptan
* Oxymetazoline
* Pergolide
* PZKKN-94 (also a 5-HT$_6$ antagonist)
* Rizatriptan
* RU-24969 (mixed 5-HT$_{1A/1B}$ agonist)
* Serotonin
* Sumatriptan
* TFMPP
* Tryptamine psychedelics (e.g., 5-MeO-DMT, DPT, psilocin/psilocybin)
* Zolmitriptan

### Partial agonists

* Asenapine
* AZ10419369
* Bromocriptine
* Metergoline
* Naphthylpiperazine
* Vortioxetine
* Ziprasidone

### Antagonists and inverse agonists

* Alprenolol
* AOP-208 (LB-208)
* AR-A000002 (AZD-8129)
* Aripiprazole
* AZD-1134
* AZD-3783
* AZ12320927
* Carteolol
* Elzasonan
* GR-55562
* GR-127935
* Isamoltane (CGP-361A)
* LY-393558
* Metitepine (methiothepin)
* NAS-181 (MCOMM)
* Oxprenolol
* Penbutolol
* Propranolol
* Risperidone
* SB-216,641
* SB-224,289 (inverse agonist)
* SB-236,057 (inverse agonist)
* SB-245,570
* SB-649,915
* Tertatolol
* Yohimbine

### Unknown

* Dextromethorphan

## Genetics

In humans the protein is coded by the gene HTR1B.
A genetic variant in the promoter region, A-161T, has been examined with respect to personality traits and showed no major effect.