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5-HT1F receptor

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Target id: 5

Nomenclature: 5-HT1F receptor

Family: 5-Hydroxytryptamine receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 366 3p12 HTR1F 5-hydroxytryptamine receptor 1F 3
Mouse 7 366 16 37.1 cM Htr1f 5-hydroxytryptamine (serotonin) receptor 1F 6
Rat 7 366 11p12 Htr1f 5-hydroxytryptamine receptor 1F 9
Previous and Unofficial Names Click here for help
5-HT1Eβ [9] | 5-HT6 | 5-HT1F | HTR1EL | serotonin receptor 1F | 5-hydroxytryptamine (serotonin) receptor 1F, G protein-coupled
Database Links Click here for help
Specialist databases
GPCRdb 5ht1f_human (Hs), 5ht1f_mouse (Mm), 5ht1f_rat (Rn)
Other databases
Alphafold P30939 (Hs), Q02284 (Mm), P30940 (Rn)
ChEMBL Target CHEMBL1805 (Hs), CHEMBL4646 (Rn)
DrugBank Target P30939 (Hs)
Ensembl Gene ENSG00000179097 (Hs), ENSMUSG00000050783 (Mm), ENSRNOG00000000716 (Rn)
Entrez Gene 3355 (Hs), 15557 (Mm), 60448 (Rn)
Human Protein Atlas ENSG00000179097 (Hs)
KEGG Gene hsa:3355 (Hs), mmu:15557 (Mm), rno:60448 (Rn)
OMIM 182134 (Hs)
Pharos P30939 (Hs)
RefSeq Nucleotide NM_000866 (Hs), NM_008310 (Mm), NM_021857 (Rn)
RefSeq Protein NP_000857 (Hs), NP_032336 (Mm), NP_068629 (Rn)
UniProtKB P30939 (Hs), Q02284 (Mm), P30940 (Rn)
Wikipedia HTR1F (Hs)
Natural/Endogenous Ligands Click here for help
5-hydroxytryptamine

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]LY334370 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist 9.4 pKd 18
⤷ pKd 9.4 (Kd 3.98x10-10 M) [18]
[125I]LSD Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Mm Agonist 9.0 pKd 4
⤷ pKd 9.0 (Kd 9.8x10-10 M) [4]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 8.0 pKd 3
⤷ pKd 8.0 [3]
BRL-54443 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 8.9 pKi 5
⤷ pKi 8.9 [5]
LY334370 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.7 pKi 18
⤷ pKi 8.7 (Ki 1.99x10-9 M) [18]
lasmiditan Small molecule or natural product Approved drug Ligand has a PDB structure Hs Full agonist 8.7 pKi 12
⤷ pKi 8.7 [12]
5-BODMT Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Agonist 8.4 pKi 8
⤷ pKi 8.4 (Ki 3.6x10-9 M) [8]
LY344864 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.2 pKi 14
⤷ pKi 8.2 (Ki 6.31x10-9 M) [14]
naratriptan Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 8.2 pKi 11,18
⤷ pKi 8.2 [11,18]
eletriptan Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Full agonist 8.0 pKi 11
⤷ pKi 8.0 (Ki 1x10-8 M) [11]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 7.7 – 8.0 pKi 1,3,18
⤷ pKi 7.7 – 8.0 [1,3,18]
sumatriptan Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.2 – 7.9 pKi 1,3,11,18
⤷ pKi 7.2 – 7.9 [1,3,11,18]
zolmitriptan Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.4 – 7.5 pKi 11,18
⤷ pKi 7.4 – 7.5 [11,18]
5-MeO-DMT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.4 pKi 3
⤷ pKi 7.4 [3]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 6.9 pKi 16
⤷ pKi 6.9 [16]
dihydroergotamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.6 – 7.1 pKi 1,18
⤷ pKi 6.6 – 7.1 [1,18]
GR 127935 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.4 – 7.2 pKi 15,18
⤷ pKi 6.4 – 7.2 [15,18]
ergotamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.8 pKi 3
⤷ pKi 6.8 [3]
NAN 190 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.7 pKi 3
⤷ pKi 6.7 [3]
α-methyl-5-HT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.7 pKi 3
⤷ pKi 6.7 [3]
rizatriptan Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 6.4 – 6.8 pKi 11,18
⤷ pKi 6.4 – 6.8 [11,18]
olanzapine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 6.5 pKi 16
⤷ pKi 6.5 [16]
xanomeline Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.5 pKi 19
⤷ pKi 6.5 [19]
2-methyl-5-HT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.4 pKi 3
⤷ pKi 6.4 [3]
5-CT Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.1 pKi 1,3
⤷ pKi 6.1 [1,3]
BRL-15572 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Partial agonist 6.0 pKi 15
⤷ pKi 6.0 [15]
TFMPP Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.0 pKi 3
⤷ pKi 6.0 [3]
5-MeOT Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.9 pKi 3
⤷ pKi 5.9 [3]
8-OH-DPAT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.8 pKi 3
⤷ pKi 5.8 [3]
dipropyl-5-CT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.8 pKi 3
⤷ pKi 5.8 [3]
DOI Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.8 pKi 3
⤷ pKi 5.8 [3]
quetiapine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 5.6 pKi 16
⤷ pKi 5.6 [16]
tryptamine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.6 pKi 3
⤷ pKi 5.6 [3]
donitriptan Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.5 pKi 7
⤷ pKi 5.5 [7]
ergotamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 7.3 pIC50 9
⤷ pIC50 7.3 [9]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 7.2 pIC50 9
⤷ pIC50 7.2 [9]
sumatriptan Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.2 pIC50 9
⤷ pIC50 7.2 [9]
5-CT Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 5.6 pIC50 9
⤷ pIC50 5.6 [9]
View species-specific agonist tables
Agonist Comments
Compared to other family members, BRL-54443 is selective for 5-HT1e and 5-HT1F receptors [5].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
methysergide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.2 pKi 3,18
⤷ pKi 8.2 [3,18]
methylergonovine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.5 pKi 3
⤷ pKi 7.5 [3]
1-naphthylpiperazine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.3 pKi 1,3
⤷ pKi 7.3 [1,3]
yohimbine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.0 pKi 3
⤷ pKi 7.0 [3]
metergoline Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.5 pKi 1,3
⤷ pKi 6.5 [1,3]
sertindole Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.4 pKi 16
⤷ pKi 6.4 [16]
methiothepin Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 1,3
⤷ pKi 6.2 [1,3]
risperidone Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.9 pKi 16
⤷ pKi 5.9 [16]
methysergide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 7.8 pIC50 9
⤷ pIC50 7.8 [9]
metergoline Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.3 pIC50 9
⤷ pIC50 6.3 [9]
yohimbine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 6.2 pIC50 9
⤷ pIC50 6.2 [9]
View species-specific antagonist tables
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
References:  2
Tissue Distribution Click here for help
Brain, uterus (endometrium and myometrium), mesentery.
Species:  Human
Technique:  PCR.
References:  3
Ventricle wall > atrium, epicardium, coronary artery.
Species:  Human
Technique:  RT-PCR.
References:  13
Brain: lamina V of the frontal cortex in large pyramidal cells, hippocampal pyramidal cells, thalamic nuclei and dorsal raphe.
Species:  Human
Technique:  in situ hybridisation.
References:  3
Trigeminal ganglion.
Species:  Rat
Technique:  Immunohistochemistry.
References:  10
Thymus, peripheral blood lymphocytes, spleen, mitogen-activated spleen cells.
Species:  Rat
Technique:  RT-PCR.
References:  17
Brain: cortex, striatum, hippocampus > thalamus, pons > hypothalamus > cerebellum.
Species:  Rat
Technique:  RT-PCR.
References:  9
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of cAMP levels in HeLa cells transfected with the rat 5-HT1f receptor.
Species:  Rat
Tissue:  HeLa cells.
Response measured:  Inhibition of cAMP accumulation.
References:  9
Measurement of cAMP levels in LM(tk-) cells
Species:  Human
Tissue:  LM(tk-) cells.
Response measured:  Weak inhibition of cAMP accumulation.
References:  3
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Htr1ftm1Dgen Htr1ftm1Dgen/Htr1ftm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:99842  MP:0009141 increased prepulse inhibition
Htr1ftm1Dgen Htr1ftm1Dgen/Htr1ftm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:99842  MP:0001973 increased thermal nociceptive threshold
General Comments
Physiological role remains unknown.

References

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1. Adham N, Bard JA, Zgombick JM, Durkin MM, Kucharewicz S, Weinshank RL, Branchek TA. (1997) Cloning and characterization of the guinea pig 5-HT1F receptor subtype: a comparison of the pharmacological profile to the human species homolog. Neuropharmacology, 36 (4-5): 569-76. [PMID:9225282]

2. Adham N, Borden LA, Schechter LE, Gustafson EL, Cochran TL, Vaysse PJ, Weinshank RL, Branchek TA. (1993) Cell-specific coupling of the cloned human 5-HT1F receptor to multiple signal transduction pathways. Naunyn Schmiedebergs Arch Pharmacol, 348 (6): 566-75. [PMID:8133900]

3. Adham N, Kao HT, Schecter LE, Bard J, Olsen M, Urquhart D, Durkin M, Hartig PR, Weinshank RL, Branchek TA. (1993) Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Proc Natl Acad Sci USA, 90 (2): 408-12. [PMID:8380639]

4. Amlaiky N, Ramboz S, Boschert U, Plassat JL, Hen R. (1992) Isolation of a mouse "5HT1E-like" serotonin receptor expressed predominantly in hippocampus. J Biol Chem, 267 (28): 19761-4. [PMID:1328180]

5. Brown AM, Avenell K, Young TJ, Ho M, Porter RA, Vimal M, Middlemiss DN. (1998) BRL 54443, a potent agonist with selectivity for human cloned 5-HT1E and 5-HT1F receptors. Br J Pharmacol, 123 (1): 233.

6. Guptan P, Dhingra A, Panicker MM. (1997) Multiple transcripts encode the 5-HT1F receptor in rodent brain. Neuroreport, 8 (15): 3317-21. [PMID:9351664]

7. John GW, Pauwels PJ, Perez M, Halazy S, Le Grand B, Verscheure Y, Valentin JP, Palmier C, Wurch T, Chopin P et al.. (1999) F 11356, a novel 5-hydroxytryptamine (5-HT) derivative with potent, selective, and unique high intrinsic activity at 5-HT1B/1D receptors in models relevant to migraine. J Pharmacol Exp Ther, 290 (1): 83-95. [PMID:10381763]

8. Klein MT, Dukat M, Glennon RA, Teitler M. (2011) Toward selective drug development for the human 5-hydroxytryptamine 1E receptor: a comparison of 5-hydroxytryptamine 1E and 1F receptor structure-affinity relationships. J Pharmacol Exp Ther, 337 (3): 860-7. [PMID:21422162]

9. Lovenberg TW, Erlander MG, Baron BM, Racke M, Slone AL, Siegel BW, Craft CM, Burns JE, Danielson PE, Sutcliffe JG. (1993) Molecular cloning and functional expression of 5-HT1E-like rat and human 5-hydroxytryptamine receptor genes. Proc Natl Acad Sci USA, 90 (6): 2184-8. [PMID:8384716]

10. Ma QP. (2001) Co-localization of 5-HT(1B/1D/1F) receptors and glutamate in trigeminal ganglia in rats. Neuroreport, 12 (8): 1589-91. [PMID:11409721]

11. Napier C, Stewart M, Melrose H, Hopkins B, McHarg A, Wallis R. (1999) 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, 368 (2-3): 259-68. [PMID:10193663]

12. Nelson DL, Phebus LA, Johnson KW, Wainscott DB, Cohen ML, Calligaro DO, Xu YC. (2010) Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan. Cephalalgia, 30 (10): 1159-69. [PMID:20855361]

13. Nilsson T, Longmore J, Shaw D, Pantev E, Bard JA, Branchek T, Edvinsson L. (1999) Characterisation of 5-HT receptors in human coronary arteries by molecular and pharmacological techniques. Eur J Pharmacol, 372 (1): 49-56. [PMID:10374714]

14. Phebus LA, Johnson KW, Zgombick JM, Gilbert PJ, Van Belle K, Mancuso V, Nelson DL, Calligaro DO, Kiefer Jr AD, Branchek TA et al.. (1997) Characterization of LY344864 as a pharmacological tool to study 5-HT1F receptors: binding affinities, brain penetration and activity in the neurogenic dural inflammation model of migraine. Life Sci, 61 (21): 2117-26. [PMID:9395253]

15. Price GW, Burton MJ, Collin LJ, Duckworth M, Gaster L, Göthert M, Jones BJ, Roberts C, Watson JM, Middlemiss DN. (1997) SB-216641 and BRL-15572--compounds to pharmacologically discriminate h5-HT1B and h5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol, 356 (3): 312-20. [PMID:9303567]

16. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE. (1996) Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl.), 124 (1-2): 57-73. [PMID:8935801]

17. Stefulj J, Jernej B, Cicin-Sain L, Rinner I, Schauenstein K. (2000) mRNA expression of serotonin receptors in cells of the immune tissues of the rat. Brain Behav Immun, 14 (3): 219-24. [PMID:10970681]

18. Wainscott DB, Krushinski Jr JH, Audia JE, Schaus JM, Zgombick JM, Lucaites VL, Nelson DL. (2005) [3H]LY334370, a novel radioligand for the 5-HT1F receptor. I. In vitro characterization of binding properties. Naunyn Schmiedebergs Arch Pharmacol, 371 (3): 169-77. [PMID:15900510]

19. Watson J, Brough S, Coldwell MC, Gager T, Ho M, Hunter AJ, Jerman J, Middlemiss DN, Riley GJ, Brown AM. (1998) Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. Br J Pharmacol, 125 (7): 1413-20. [PMID:9884068]

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