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 Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42]
Aggressive non-hodgkin's lymphoma [ICD9: 200, 201, 202, 202.8, 208.9; ICD10: C81, C81-C86, C82-C85, C91-C95]
Chronic schizophrenics [ICD9: 295; ICD10: F20]
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]
Migraine [ICD9: 346; ICD10: G43]
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 [1]
Eletriptan Drug Info Approved Migraine [2], [3]
Fluphenazine Drug Info Approved Psychotic disorders [4], [5]
Frovatriptan Drug Info Approved Migraine headaches [2], [6]
Naratriptan Drug Info Approved Migraine headaches [7], [2]
Prolixin decanoate Drug Info Approved Chronic schizophrenics [8]
Zolmitriptan Drug Info Approved Migraine [9], [10]
Eltoprazine Drug Info Phase 2 Aggressive non-hodgkin's lymphoma [11]
NXN-188 Drug Info Phase 2 Migraine [12]
[N-methyl-3H(3)]AZ-10419369 Drug Info Phase 1 Mood disorder [13], [14]
Donitriptan Drug Info Preclinical Migraine [15], [16]
Elzasonan hydrochloride Drug Info Discontinued in Phase 2 Severe mood disorders [17]
IS-159 Drug Info Discontinued in Phase 2 Migraine [18]
Anpirtoline Drug Info Terminated Pain [19]
AZD-1134 Drug Info Terminated Anxiety disorder [20]
CGS-12066B Drug Info Terminated Anxiety disorder [21], [22]
F-12682 Drug Info Terminated Major depressive disorder [23]
GR-127935 Drug Info Terminated Major depressive disorder [24], [25]
L-775606 Drug Info Terminated Discovery agent [26], [27]
VR-147 Drug Info Terminated Migraine [28]
Inhibitor (+/-)-nantenine Drug Info [29]
1-(3-(pentafluorosulfanyl)phenyl)propan-2-amine Drug Info [30]
1-(7-Methoxy-naphthalen-2-yl)-piperazine Drug Info [31]
1-Naphthalen-2-yl-piperazine Drug Info [31]
2-(5-Thiophen-2-yl-1H-indol-3-yl)-ethylamine Drug Info [32]
5-amino-3-(N-methylpiperidin-4-yl)-1H-indole Drug Info [33]
5-Ethyl-3-(2-pyrrolidin-1-yl-ethyl)-1H-indole Drug Info [34]
5-Isopropyl-3-(2-pyrrolidin-1-yl-ethyl)-1H-indole Drug Info [34]
A-987306 Drug Info [35]
L-747201 Drug Info [36]
L-775606 Drug Info [36]
SEROTONIN Drug Info [35]
WAY-466 Drug Info [37]
[2-(5-Ethyl-1H-indol-3-yl)-ethyl]-dimethyl-amine Drug Info [34]
Antagonist (R)-flurocarazolol Drug Info [38]
(S)-flurocarazolol Drug Info [38]
5-OH-DPAT Drug Info [39]
9-OH-risperidone Drug Info [40]
AZD-1134 Drug Info [41], [1]
F-12682 Drug Info [42], [1]
GR55562 Drug Info [43]
metergoline Drug Info [44]
SB 224289 Drug Info [43]
SB 272183 Drug Info [45]
SB 649915 Drug Info [46]
SB 714786 Drug Info [46]
SB236057 Drug Info [47]
[3H]GR 125,743 Drug Info [48]
[N-methyl-3H(3)]AZ-10419369 Drug Info [49], [1]
Agonist 1-naphthylpiperazine Drug Info [44]
2-methyl-5-HT Drug Info [50]
5-(nonyloxy)-tryptamine Drug Info [51]
5-CT Drug Info [39]
7-methoxy-1-naphthylpiperazine Drug Info [31]
BRL-15572 Drug Info [52]
CP-94,253 Drug Info [53]
dipropyl-5-CT Drug Info [50]
Eltoprazine Drug Info [54], [1]
L-772,405 Drug Info [55]
lysergol Drug Info [44]
Naratriptan Drug Info [56]
SB 216641 Drug Info [52]
SB 236057-A Drug Info [57]
TFMPP Drug Info [44]
[11C]AZ10419369 Drug Info [58]
[125I]GTI Drug Info [59]
[3H]8-OH-DPAT Drug Info [60]
[3H]alniditan Drug Info [61]
[3H]eletriptan Drug Info [62]
[3H]sumatriptan Drug Info [62]
Modulator Anpirtoline Drug Info [19]
CGS-12066B Drug Info
Dihydroergotamine nasal Drug Info [61]
Donitriptan Drug Info
Eletriptan Drug Info [63]
Elzasonan hydrochloride Drug Info
Fluphenazine Drug Info [63]
Frovatriptan Drug Info [63]
GR-127935 Drug Info
IS-159 Drug Info
NXN-188 Drug Info
Prolixin decanoate Drug Info [63]
VR-147 Drug Info [64], [1]
Zolmitriptan Drug Info [63]
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
REF 1Sustained 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 6(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).
REF 7(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: 45).
REF 8FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 016727.
REF 9FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020768.
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REF 12ClinicalTrials.gov (NCT00920686) Study of NXN 188 for the Treatment of Migraine With Aura. U.S. National Institutes of Health.
REF 13ClinicalTrials.gov (NCT01085123) Determine Central 5-HT1B Receptor Occupancy of ZOMIG Rapimelt (Zolmitriptan) in Healthy Male Volunteers. U.S. National Institutes of Health.
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REF 33J 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 34Bioorg Med Chem Lett. 2000 Aug 7;10(15):1707-9.5-Alkyltryptamine derivatives as highly selective and potent 5-HT1D receptor agonists.
REF 35J 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 38The 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.
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REF 40Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73.
REF 41N-methyl-3H3AZ10419369 binding to the 5-HT1B receptor: in vitro characterization and in vivo receptor occupancy. J Pharmacol Exp Ther. 2009 Jul;330(1):342-51.
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REF 435-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 44Two 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 45SB-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 46Discovery of the first potent, selective 5-hydroxytryptamine1D receptor antagonist. J Med Chem. 2005 May 19;48(10):3478-80.
REF 47SB-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 48Serotonin 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 495-HT1B and other related serotonergic proteins are altered in APPswe mutation. Neurosci Lett. 2015 May 6;594:137-43.
REF 50Human 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 51Identification 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 52SB-216641 and BRL-15572--compounds to pharmacologically discriminate h5-HT1B and h5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):312-20.
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