Target Information

Target General Infomation
Target ID
T07806
Former ID
TTDS00099
Target Name
5-hydroxytryptamine 1B receptor
Gene Name
HTR1B
Synonyms
5-HT-1B; 5-HT-1D-beta; 5-HT1B receptor; S12; Serotonin 1D beta receptor; Serotonin receptor; Serotonin receptor 1B; HTR1B
Target Type
Successful
Disease Aggressive non-hodgkin's lymphoma [ICD9: 200, 201, 202, 202.8, 208.9; ICD10: C81, C81-C86, C82-C85, C91-C95]
Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42]
Chronic schizophrenics [ICD9: 295; ICD10: F20]
Migraine [ICD9: 346; ICD10: G43]
Migraine headaches [ICD9: 346; ICD10: G43]
Major depressive disorder [ICD9: 296.2, 296.3, 710.0; ICD10: F32, F33, M32]
Mood disorder [ICD10: F30-F39]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
Psychotic disorders [ICD9: 290-299; ICD10: F20-F29]
Severe mood disorders [ICD9: 296; ICD10: F30-F39]
Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.
BioChemical Class
GPCR rhodopsin
Target Validation
T07806
UniProt ID
P28222
Sequence
MEEPGAQCAPPPPAGSETWVPQANLSSAPSQNCSAKDYIYQDSISLPWKVLLVMLLALIT
LATTLSNAFVIATVYRTRKLHTPANYLIASLAVTDLLVSILVMPISTMYTVTGRWTLGQV
VCDFWLSSDITCCTASILHLCVIALDRYWAITDAVEYSAKRTPKRAAVMIALVWVFSISI
SLPPFFWRQAKAEEEVSECVVNTDHILYTVYSTVGAFYFPTLLLIALYGRIYVEARSRIL
KQTPNRTGKRLTRAQLITDSPGSTSSVTSINSRVPDVPSESGSPVYVNQVKVRVSDALLE
KKKLMAARERKATKTLGIILGAFIVCWLPFFIISLVMPICKDACWFHLAIFDFFTWLGYL
NSLINPIIYTMSNEDFKQAFHKLIRFKCTS
Drugs and Mode of Action
Drug(s) Dihydroergotamine nasal Drug Info Approved Migraine [551730]
Eletriptan Drug Info Approved Migraine [536361], [540615]
Fluphenazine Drug Info Approved Psychotic disorders [536507], [539303]
Frovatriptan Drug Info Approved Migraine headaches [536361], [542203]
Naratriptan Drug Info Approved Migraine headaches [467741], [536361]
Prolixin decanoate Drug Info Approved Chronic schizophrenics [538477]
Zolmitriptan Drug Info Approved Migraine [538555], [541265]
Eltoprazine Drug Info Phase 2 Aggressive non-hodgkin's lymphoma [523309]
NXN-188 Drug Info Phase 2 Migraine [522692]
[N-methyl-3H(3)]AZ-10419369 Drug Info Phase 1 Mood disorder [522971], [540197]
Donitriptan Drug Info Preclinical Migraine [540538], [547009]
Elzasonan hydrochloride Drug Info Discontinued in Phase 2 Severe mood disorders [536580]
IS-159 Drug Info Discontinued in Phase 2 Migraine [545995]
Anpirtoline Drug Info Terminated Pain [528148]
AZD-1134 Drug Info Terminated Anxiety disorder [547616]
CGS-12066B Drug Info Terminated Anxiety disorder [538669], [546046]
F-12682 Drug Info Terminated Major depressive disorder [546890]
GR-127935 Drug Info Terminated Major depressive disorder [538876], [545301]
L-775606 Drug Info Terminated Discovery agent [538680], [546600]
VR-147 Drug Info Terminated Migraine [548264]
Inhibitor (+/-)-nantenine Drug Info [530558]
1-(3-(pentafluorosulfanyl)phenyl)propan-2-amine Drug Info [529013]
1-(7-Methoxy-naphthalen-2-yl)-piperazine Drug Info [534528]
1-Naphthalen-2-yl-piperazine Drug Info [534528]
2-(5-Thiophen-2-yl-1H-indol-3-yl)-ethylamine Drug Info [525792]
5-amino-3-(N-methylpiperidin-4-yl)-1H-indole Drug Info [529496]
5-Ethyl-3-(2-pyrrolidin-1-yl-ethyl)-1H-indole Drug Info [525845]
5-Isopropyl-3-(2-pyrrolidin-1-yl-ethyl)-1H-indole Drug Info [525845]
A-987306 Drug Info [529789]
L-747201 Drug Info [534500]
L-775606 Drug Info [534500]
SEROTONIN Drug Info [529789]
WAY-466 Drug Info [527381]
[2-(5-Ethyl-1H-indol-3-yl)-ethyl]-dimethyl-amine Drug Info [525845]
Antagonist (R)-flurocarazolol Drug Info [526124]
(S)-flurocarazolol Drug Info [526124]
5-OH-DPAT Drug Info [527317]
9-OH-risperidone Drug Info [534281]
AZD-1134 Drug Info [530096], [551730]
F-12682 Drug Info [546891], [551730]
GR55562 Drug Info [534909]
metergoline Drug Info [534239]
SB 224289 Drug Info [534909]
SB 272183 Drug Info [526100]
SB 649915 Drug Info [527551]
SB 714786 Drug Info [527551]
SB236057 Drug Info [525557]
[3H]GR 125,743 Drug Info [525563]
[N-methyl-3H(3)]AZ-10419369 Drug Info [533202], [551730]
Agonist 1-naphthylpiperazine Drug Info [534239]
2-methyl-5-HT Drug Info [527380]
5-(nonyloxy)-tryptamine Drug Info [525602]
5-CT Drug Info [527317]
7-methoxy-1-naphthylpiperazine Drug Info [534528]
BRL-15572 Drug Info [534475]
CP-94,253 Drug Info [535394]
dipropyl-5-CT Drug Info [527380]
Eltoprazine Drug Info [551057], [551730]
L-772,405 Drug Info [525646]
lysergol Drug Info [534239]
Naratriptan Drug Info [536607]
SB 216641 Drug Info [534475]
SB 236057-A Drug Info [535363]
TFMPP Drug Info [534239]
[11C]AZ10419369 Drug Info [530875]
[125I]GTI Drug Info [533994]
[3H]8-OH-DPAT Drug Info [525553]
[3H]alniditan Drug Info [534635]
[3H]eletriptan Drug Info [525461]
[3H]sumatriptan Drug Info [525461]
Modulator Anpirtoline Drug Info [528148]
CGS-12066B Drug Info
Dihydroergotamine nasal Drug Info [534635]
Donitriptan Drug Info
Eletriptan Drug Info [556264]
Elzasonan hydrochloride Drug Info
Fluphenazine Drug Info [556264]
Frovatriptan Drug Info [556264]
GR-127935 Drug Info
IS-159 Drug Info
NXN-188 Drug Info
Prolixin decanoate Drug Info [556264]
VR-147 Drug Info [550903], [551730]
Zolmitriptan Drug Info [556264]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway cAMP signaling pathway
Neuroactive ligand-receptor interaction
Serotonergic synapse
PANTHER Pathway Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway
5HT1 type receptor mediated signaling pathway
Reactome Serotonin receptors
G alpha (i) signalling events
WikiPathways Serotonin HTR1 Group and FOS Pathway
Monoamine GPCRs
GPCRs, Class A Rhodopsin-like
GPCR ligand binding
GPCR downstream signaling
References
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Ref 522692ClinicalTrials.gov (NCT00920686) Study of NXN 188 for the Treatment of Migraine With Aura. U.S. National Institutes of Health.
Ref 522971ClinicalTrials.gov (NCT01085123) Determine Central 5-HT1B Receptor Occupancy of ZOMIG Rapimelt (Zolmitriptan) in Healthy Male Volunteers. U.S. National Institutes of Health.
Ref 523309ClinicalTrials.gov (NCT01266174) Effects of Eltoprazine on Cognitive Impairment Associated With Schizophrenia (CIAS) in Adults. U.S. National Institutes of Health.
Ref 528148Effects of anpirtoline on regional serotonin synthesis in the rat brain: an autoradiographic study. Nucl Med Biol. 2006 Apr;33(3):325-32. Epub 2006 Mar 9.
Ref 536361Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
Ref 536507The antipsychotic drug, fluphenazine, effectively reverses mechanical allodynia in rat models of neuropathic pain. Psychopharmacology (Berl). 2008 Jan;195(4):559-68. Epub 2007 Sep 23.
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Ref 538555FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020768.
Ref 538669(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 109).
Ref 538680(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 114).
Ref 538876(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 14).
Ref 539303(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 204).
Ref 540197(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3219).
Ref 540538(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 39).
Ref 540615(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 40).
Ref 541265(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 60).
Ref 542203(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7191).
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Ref 525461Characterisation of the 5-HT receptor binding profile of eletriptan and kinetics of [3H]eletriptan binding at human 5-HT1B and 5-HT1D receptors. Eur J Pharmacol. 1999 Mar 5;368(2-3):259-68.
Ref 525553Actions of roxindole at recombinant human dopamine D2, D3 and D4 and serotonin 5-HT1A, 5-HT1B and 5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol. 1999 Jun;359(6):447-53.
Ref 525557SB-236057, a selective 5-HT1B receptor inverse agonist, blocks the 5-HT human terminal autoreceptor. Eur J Pharmacol. 1999 Jun 30;375(1-3):359-65.
Ref 525563Serotonin 5-HT1B and 5-HT1D receptors form homodimers when expressed alone and heterodimers when co-expressed. FEBS Lett. 1999 Jul 30;456(1):63-7.
Ref 525602Identification of an amino acid residue important for binding of methiothepin and sumatriptan to the human 5-HT(1B) receptor. Eur J Pharmacol. 1999 Sep 10;380(2-3):171-81.
Ref 5256463-[3-(Piperidin-1-yl)propyl]indoles as highly selective h5-HT(1D) receptor agonists. J Med Chem. 1999 Dec 2;42(24):4981-5001.
Ref 525792Bioorg Med Chem Lett. 2000 May 1;10(9):903-5.5-Thienyltryptamine derivatives as serotonin 5-HT1B/1D receptor agonists: potential treatments for migraine.
Ref 525845Bioorg Med Chem Lett. 2000 Aug 7;10(15):1707-9.5-Alkyltryptamine derivatives as highly selective and potent 5-HT1D receptor agonists.
Ref 526100SB-272183, a selective 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptor antagonist in native tissue. Br J Pharmacol. 2001 Jul;133(6):797-806.
Ref 526124The in vitro pharmacology of the beta-adrenergic receptor pet ligand (s)-fluorocarazolol reveals high affinity for cloned beta-adrenergic receptors and moderate affinity for the human 5-HT1A receptor. Psychopharmacology (Berl). 2001 Aug;157(1):111-4.
Ref 527317Mouse 5HT1B serotonin receptor: cloning, functional expression, and localization in motor control centers. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3020-4.
Ref 527380Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3630-4.
Ref 527381J Med Chem. 2005 Jan 27;48(2):353-6.Discovery of 5-arylsulfonamido-3-(pyrrolidin-2-ylmethyl)-1H-indole derivatives as potent, selective 5-HT6 receptor agonists and antagonists.
Ref 527551Discovery of the first potent, selective 5-hydroxytryptamine1D receptor antagonist. J Med Chem. 2005 May 19;48(10):3478-80.
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Ref 529013Bioorg Med Chem. 2007 Nov 1;15(21):6659-66. Epub 2007 Aug 15.The synthesis and biological activity of pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine.
Ref 529496J Med Chem. 2008 Jun 26;51(12):3609-16. Epub 2008 May 29.Designing selective, high affinity ligands of 5-HT1D receptor by covalent dimerization of 5-HT1F ligands derived from 4-fluoro-N-[3-(1-methyl-4-piperidinyl)-1H-indol-5-yl]benzamide.
Ref 529789J Med Chem. 2008 Nov 27;51(22):7094-8.cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia.
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Ref 530558Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. Epub 2009 Nov 20.Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine.
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Ref 5332025-HT1B and other related serotonergic proteins are altered in APPswe mutation. Neurosci Lett. 2015 May 6;594:137-43.
Ref 533994Autoradiographic characterisation and localisation of 5-HT1D compared to 5-HT1B binding sites in rat brain. Naunyn Schmiedebergs Arch Pharmacol. 1993 Jun;347(6):569-82.
Ref 534239Two amino acid differences in the sixth transmembrane domain are partially responsible for the pharmacological differences between the 5-HT1D beta and 5-HT1E 5-hydroxytryptamine receptors. J Neurochem. 1996 Nov;67(5):2096-103.
Ref 534281Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73.
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Ref 534500J Med Chem. 1997 Oct 24;40(22):3501-3.Selective, orally active 5-HT1D receptor agonists as potential antimigraine agents.
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Ref 534635Br J Pharmacol. 1998 Apr;123(8):1655-65.Agonistic properties of alniditan, sumatriptan and dihydroergotamine on human 5-HT1B and 5-HT1D receptors expressed in various mammalian cell lines.
Ref 5349095-hydroxytryptamine receptors mediating contraction in human small muscular pulmonary arteries: importance of the 5-HT1B receptor. Br J Pharmacol. 1999 Oct;128(3):730-4.
Ref 535363SB-236057-A: a selective 5-HT1B receptor inverse agonist. CNS Drug Rev. 2001 Winter;7(4):433-44.
Ref 535394Anxiogenic-like effect of serotonin(1B) receptor stimulation in the rat elevated plus-maze. Pharmacol Biochem Behav. 2002 Apr;71(4):581-7.
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Ref 550903US patent application no. 2010,0112,050, Dosage form for insertion into the mouth.
Ref 551057Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.
Ref 551730Sustained pain relief with dihydroergotamine in migraine is potentially due to persistent binding to 5-HT1B and 5-HT1D receptors. . The Journal of Headache and Pain 201314(Suppl 1):P75.
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Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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