Target Information

Target General Information

Target ID

T07806 (Former ID: TTDS00099)

Target Name

5-HT 1B receptor (HTR1B)

Synonyms

Serotonin receptor 1B; Serotonin 1D beta receptor; S12; HTR1DB; 5-hydroxytryptamine receptor 1B; 5-HT1B receptor; 5-HT1B; 5-HT-1D-beta; 5-HT-1B

Gene Name

HTR1B

Target Type

Successful target

[1]

Disease

[+] 4 Target-related Diseases

Migraine [ICD-11: 8A80]

Pituitary gland disorder [ICD-11: 5A60-5A61]

Psychotic disorder [ICD-11: 6A20-6A25]

Schizophrenia [ICD-11: 6A20]

Function

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. G-protein coupled receptor for 5-hydroxytryptamine (serotonin).

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BioChemical Class

GPCR rhodopsin

UniProt ID

5HT1B_HUMAN

Sequence

MEEPGAQCAPPPPAGSETWVPQANLSSAPSQNCSAKDYIYQDSISLPWKVLLVMLLALIT
LATTLSNAFVIATVYRTRKLHTPANYLIASLAVTDLLVSILVMPISTMYTVTGRWTLGQV
VCDFWLSSDITCCTASILHLCVIALDRYWAITDAVEYSAKRTPKRAAVMIALVWVFSISI
SLPPFFWRQAKAEEEVSECVVNTDHILYTVYSTVGAFYFPTLLLIALYGRIYVEARSRIL
KQTPNRTGKRLTRAQLITDSPGSTSSVTSINSRVPDVPSESGSPVYVNQVKVRVSDALLE
KKKLMAARERKATKTLGIILGAFIVCWLPFFIISLVMPICKDACWFHLAIFDFFTWLGYL
NSLINPIIYTMSNEDFKQAFHKLIRFKCTS

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

HIT2.0 ID

T97ZTQ

Drugs and Modes of Action

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Approved Drug(s)

[+] 7 Approved Drugs

Eletriptan

Drug Info

Approved

Migraine

[2], [3]

Fluphenazine

Drug Info

Approved

Psychotic disorder

[4], [5]

Frovatriptan

Drug Info

Approved

Migraine

[3], [6]

Metergolin

Drug Info

Approved

Hyperprolactinaemia

[7]

Naratriptan

Drug Info

Approved

Migraine

[3], [8]

Prolixin decanoate

Drug Info

Approved

Schizophrenia

[9]

Zolmitriptan

Drug Info

Approved

Migraine

[10], [11]

Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

Eltoprazine

Drug Info

Phase 3

Attention deficit hyperactivity disorder

[12]

NXN-188

Drug Info

Phase 2

Migraine

[13]

[N-methyl-3H(3)]AZ-10419369

Drug Info

Phase 1

Mood disorder

[14], [15]

Discontinued Drug(s)

[+] 9 Discontinued Drugs

Alniditan

Drug Info

Discontinued in Phase 3

Migraine

[16], [17]

Elzasonan hydrochloride

Drug Info

Discontinued in Phase 2

Mood disorder

[18]

IS-159

Drug Info

Discontinued in Phase 2

Migraine

[19]

Anpirtoline

Drug Info

Terminated

Pain

[22]

AZD-1134

Drug Info

Terminated

Anxiety disorder

[23]

CGS-12066B

Drug Info

Terminated

Anxiety disorder

[24], [25]

F-12682

Drug Info

Terminated

Major depressive disorder

[26]

GR-127935

Drug Info

Terminated

Major depressive disorder

[27], [28]

VR-147

Drug Info

Terminated

Migraine

[29]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

Donitriptan

Drug Info

Preclinical

Migraine

[20], [21]

Mode of Action

[+] 4 Modes of Action

Modulator

[+] 13 Modulator drugs

Eletriptan

Drug Info

[30]

Fluphenazine

Drug Info

[30]

Frovatriptan

Drug Info

[30]

Prolixin decanoate

Drug Info

[30]

Zolmitriptan

Drug Info

[30]

NXN-188

Drug Info

[34]

Elzasonan hydrochloride

Drug Info

[37]

IS-159

Drug Info

[38]

Donitriptan

Drug Info

[39]

Anpirtoline

Drug Info

[22]

CGS-12066B

Drug Info

[41]

GR-127935

Drug Info

[43]

VR-147

Drug Info

[33], [45]

Antagonist

[+] 15 Antagonist drugs

Metergolin

Drug Info

[31]

[N-methyl-3H(3)]AZ-10419369

Drug Info

[33], [35]

AZD-1134

Drug Info

[33], [40]

F-12682

Drug Info

[33], [42]

(R)-flurocarazolol

Drug Info

[47]

(S)-flurocarazolol

Drug Info

[47]

5-OH-DPAT

Drug Info

[54]

9-OH-risperidone

Drug Info

[56]

GR55562

Drug Info

[60]

SB 224289

Drug Info

[60]

SB 272183

Drug Info

[62]

SB 649915

Drug Info

[63]

SB 714786

Drug Info

[63]

SB236057

Drug Info

[64], [65]

[3H]GR 125,743

Drug Info

[71]

Agonist

[+] 20 Agonist drugs

Naratriptan

Drug Info

[1]

Eltoprazine

Drug Info

[32], [33]

Alniditan

Drug Info

[36]

1-naphthylpiperazine

Drug Info

[31]

2-(5-Nonyloxy-1H-indol-3-yl)-ethylamine

Drug Info

[50]

2-methyl-5-HT

Drug Info

[52]

5-CT

Drug Info

[54]

7-methoxy-1-naphthylpiperazine

Drug Info

[49]

BRL-15572

Drug Info

[58]

CP-94,253

Drug Info

[59]

dipropyl-5-CT

Drug Info

[52]

L-772,405

Drug Info

[61]

lysergol

Drug Info

[31]

SB 216641

Drug Info

[58]

TFMPP

Drug Info

[31]

[11C]AZ10419369

Drug Info

[67]

[125I]GTI

Drug Info

[68]

[3H]8-OH-DPAT

Drug Info

[69]

[3H]eletriptan

Drug Info

[70]

[3H]sumatriptan

Drug Info

[70]

Inhibitor

[+] 14 Inhibitor drugs

L-775606

Drug Info

[44]

(+/-)-nantenine

Drug Info

[46]

1-(3-(pentafluorosulfanyl)phenyl)propan-2-amine

Drug Info

[48]

1-(7-Methoxy-naphthalen-2-yl)-piperazine

Drug Info

[49]

1-Naphthalen-2-yl-piperazine

Drug Info

[49]

2-(5-Thiophen-2-yl-1H-indol-3-yl)-ethylamine

Drug Info

[51]

5-amino-3-(N-methylpiperidin-4-yl)-1H-indole

Drug Info

[53]

5-Ethyl-3-(2-pyrrolidin-1-yl-ethyl)-1H-indole

Drug Info

[55]

5-Isopropyl-3-(2-pyrrolidin-1-yl-ethyl)-1H-indole

Drug Info

[55]

A-987306

Drug Info

[57]

L-747201

Drug Info

[44]

SEROTONIN

Drug Info

[57]

WAY-466

Drug Info

[66]

[2-(5-Ethyl-1H-indol-3-yl)-ethyl]-dimethyl-amine

Drug Info

[55]

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

Top

Target-regulating microRNAs

Target-regulating microRNAs Info

Target Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

Top

KEGG Pathway

[+] 3 KEGG Pathways

cAMP signaling pathway

Neuroactive ligand-receptor interaction

Serotonergic synapse

Panther Pathway

[+] 2 Panther Pathways

Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway

5HT1 type receptor mediated signaling pathway

Reactome

[+] 2 Reactome Pathways

Serotonin receptors

G alpha (i) signalling events

WikiPathways

[+] 5 WikiPathways

Serotonin HTR1 Group and FOS Pathway

Monoamine GPCRs

GPCRs, Class A Rhodopsin-like

GPCR ligand binding

GPCR downstream signaling

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

REF 1

Triptans in pregnancy. Ther Drug Monit. 2008 Feb;30(1):5-9.

REF 2

URL: 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 3

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 4

REF 5

The antipsychotic drug, fluphenazine, effectively reverses mechanical allodynia in rat models of neuropathic pain. Psychopharmacology (Berl). 2008 Jan;195(4):559-68.

REF 6

REF 7

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 8

REF 9

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 016727.

REF 10

REF 11

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020768.

REF 12

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 13

ClinicalTrials.gov (NCT00920686) Study of NXN 188 for the Treatment of Migraine With Aura. U.S. National Institutes of Health.

REF 14

REF 15

ClinicalTrials.gov (NCT01085123) Determine Central 5-HT1B Receptor Occupancy of ZOMIG Rapimelt (Zolmitriptan) in Healthy Male Volunteers. U.S. National Institutes of Health.

REF 16

REF 17

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006286)

REF 18

Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.

REF 19

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005786)

REF 20

REF 21

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012002)

REF 22

Effects of anpirtoline on regional serotonin synthesis in the rat brain: an autoradiographic study. Nucl Med Biol. 2006 Apr;33(3):325-32.

REF 23

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017898)

REF 24

REF 25

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006033)

REF 26

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010898)

REF 27

REF 28

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002743)

REF 29

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023937)

REF 30

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

REF 31

Two 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 32

Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.

REF 33

Sustained 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.

REF 34

Company report (NeurAxon)

REF 35

5-HT1B and other related serotonergic proteins are altered in APPswe mutation. Neurosci Lett. 2015 May 6;594:137-43.

REF 36

Agonistic properties of alniditan, sumatriptan and dihydroergotamine on human 5-HT1B and 5-HT1D receptors expressed in various mammalian cell lines. Br J Pharmacol. 1998 Apr;123(8):1655-65.

REF 37

DOI: 10.1002/9781118541203.xen439

REF 38

Pronounced effect of caprylocaproyl macrogolglycerides on nasal absorption of IS-159, a peptide serotonin 1B/1D-receptor agonist. Clin Pharmacol Ther. 2000 Aug;68(2):114-21.

REF 39

Donitriptan, but not sumatriptan, inhibits capsaicin-induced canine external carotid vasodilatation via 5-HT1B rather than 5-HT1D receptors.Br J Pharmacol.2006 Sep;149(1):82-91.

REF 40

N-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.

REF 41

Biochemical and pharmacological characterization of CGS 12066B, a selective serotonin-1B agonist. Eur J Pharmacol. 1987 Apr 7;136(1):1-9.

REF 42

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010898)

REF 43

GR127935: a potent and selective 5-HT1D receptor antagonist.Behav Brain Res.1996;73(1-2):157-61.

REF 44

Selective, orally active 5-HT1D receptor agonists as potential antimigraine agents. J Med Chem. 1997 Oct 24;40(22):3501-3.

REF 45

US patent application no. 2010,0112,050, Dosage form for insertion into the mouth.

REF 46

Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31.

REF 47

The 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 48

The synthesis and biological activity of pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine. Bioorg Med Chem. 2007 Nov 1;15(21):6659-66.

REF 49

5-HT1B receptor antagonist properties of novel arylpiperazide derivatives of 1-naphthylpiperazine. J Med Chem. 1997 Nov 21;40(24):3974-8.

REF 50

Identification 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 51

5-Thienyltryptamine derivatives as serotonin 5-HT1B/1D receptor agonists: potential treatments for migraine. Bioorg Med Chem Lett. 2000 May 1;10(9):903-5.

REF 52

Human 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 53

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-pip... J Med Chem. 2008 Jun 26;51(12):3609-16.

REF 54

Mouse 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 55

5-Alkyltryptamine derivatives as highly selective and potent 5-HT1D receptor agonists. Bioorg Med Chem Lett. 2000 Aug 7;10(15):1707-9.

REF 56

Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73.

REF 57

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... J Med Chem. 2008 Nov 27;51(22):7094-8.

REF 58

SB-216641 and BRL-15572--compounds to pharmacologically discriminate h5-HT1B and h5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):312-20.

REF 59

Anxiogenic-like effect of serotonin(1B) receptor stimulation in the rat elevated plus-maze. Pharmacol Biochem Behav. 2002 Apr;71(4):581-7.

REF 60

5-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 61

3-[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 62

SB-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 63

Discovery of the first potent, selective 5-hydroxytryptamine1D receptor antagonist. J Med Chem. 2005 May 19;48(10):3478-80.

REF 64

SB-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 65

SB-236057-A: a selective 5-HT1B receptor inverse agonist. CNS Drug Rev. 2001 Winter;7(4):433-44.

REF 66

Discovery of 5-arylsulfonamido-3-(pyrrolidin-2-ylmethyl)-1H-indole derivatives as potent, selective 5-HT6 receptor agonists and antagonists. J Med Chem. 2005 Jan 27;48(2):353-6.

REF 67

Quantitative analysis of [11C]AZ10419369 binding to 5-HT1B receptors in human brain. J Cereb Blood Flow Metab. 2011 Jan;31(1):113-23.

REF 68

Autoradiographic 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 69

Actions 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 70

Characterisation 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 71

Serotonin 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.

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