5-HT<sub>1F</sub> receptor | 5-Hydroxytryptamine receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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5-HT1F receptor

Target not currently curated in GtoImmuPdb

Target id: 5

Nomenclature: 5-HT1F receptor

Family: 5-Hydroxytryptamine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
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 C1.3 Htr1f 5-hydroxytryptamine (serotonin) receptor 1F 6
Rat 7 366 11p12 Htr1f 5-hydroxytryptamine receptor 1F 9
Previous and Unofficial Names
5-HT1Eβ [9] | 5-HT6 | 5-HT1F | HTR1EL | serotonin receptor 1F | 5-hydroxytryptamine (serotonin) receptor 1F, G protein-coupled
Database Links
Specialist databases
GPCRDB 5ht1f_human (Hs), 5ht1f_mouse (Mm), 5ht1f_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
5-hydroxytryptamine

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]LY334370 Hs Full agonist 9.4 pKd 18
pKd 9.4 (Kd 3.98x10-10 M) [18]
[125I]LSD Mm Agonist 9.0 pKd 4
pKd 9.0 (Kd 9.8x10-10 M) [4]
5-hydroxytryptamine Hs Full agonist 8.0 pKd 3
pKd 8.0 [3]
BRL-54443 Hs Full agonist 8.9 pKi 5
pKi 8.9 [5]
LY334370 Hs Full agonist 8.7 pKi 18
pKi 8.7 (Ki 1.99x10-9 M) [18]
lasmiditan Hs Full agonist 8.7 pKi 12
pKi 8.7 [12]
5-BODMT Hs Agonist 8.4 pKi 8
pKi 8.4 (Ki 3.6x10-9 M) [8]
LY344864 Hs Full agonist 8.2 pKi 14
pKi 8.2 (Ki 6.31x10-9 M) [14]
naratriptan Hs Full agonist 8.2 pKi 11,18
pKi 8.2 [11,18]
eletriptan Hs Full agonist 8.0 pKi 11
pKi 8.0 (Ki 1x10-8 M) [11]
5-hydroxytryptamine Hs Full agonist 7.7 – 8.0 pKi 1,3,18
pKi 7.7 – 8.0 [1,3,18]
sumatriptan Hs Full agonist 7.2 – 7.9 pKi 1,3,11,18
pKi 7.2 – 7.9 [1,3,11,18]
zolmitriptan Hs Full agonist 7.4 – 7.5 pKi 11,18
pKi 7.4 – 7.5 [11,18]
5-MeO-DMT Hs Full agonist 7.4 pKi 3
pKi 7.4 [3]
clozapine Hs Full agonist 6.9 pKi 16
pKi 6.9 [16]
dihydroergotamine Hs Full agonist 6.6 – 7.1 pKi 1,18
pKi 6.6 – 7.1 [1,18]
GR 127935 Hs Partial agonist 6.4 – 7.2 pKi 15,18
pKi 6.4 – 7.2 [15,18]
ergotamine Hs Full agonist 6.8 pKi 3
pKi 6.8 [3]
NAN 190 Hs Partial agonist 6.7 pKi 3
pKi 6.7 [3]
α-methyl-5-HT Hs Full agonist 6.7 pKi 3
pKi 6.7 [3]
rizatriptan Hs Full agonist 6.4 – 6.8 pKi 11,18
pKi 6.4 – 6.8 [11,18]
olanzapine Hs Full agonist 6.5 pKi 16
pKi 6.5 [16]
xanomeline Hs Full agonist 6.5 pKi 19
pKi 6.5 [19]
2-methyl-5-HT Hs Full agonist 6.4 pKi 3
pKi 6.4 [3]
5-CT Hs Full agonist 6.1 pKi 1,3
pKi 6.1 [1,3]
BRL-15572 Hs Partial agonist 6.0 pKi 15
pKi 6.0 [15]
TFMPP Hs Full agonist 6.0 pKi 3
pKi 6.0 [3]
5-MeOT Hs Full agonist 5.9 pKi 3
pKi 5.9 [3]
8-OH-DPAT Hs Full agonist 5.8 pKi 3
pKi 5.8 [3]
dipropyl-5-CT Hs Full agonist 5.8 pKi 3
pKi 5.8 [3]
DOI Hs Full agonist 5.8 pKi 3
pKi 5.8 [3]
quetiapine Hs Full agonist 5.6 pKi 16
pKi 5.6 [16]
tryptamine Hs Full agonist 5.6 pKi 3
pKi 5.6 [3]
donitriptan Hs Full agonist 5.5 pKi 7
pKi 5.5 [7]
ergotamine Rn Full agonist 7.3 pIC50 9
pIC50 7.3 [9]
5-hydroxytryptamine Rn Full agonist 7.2 pIC50 9
pIC50 7.2 [9]
sumatriptan Hs Full agonist 7.2 pIC50 9
pIC50 7.2 [9]
5-CT 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 Hs Antagonist 8.2 pKi 3,18
pKi 8.2 [3,18]
methylergonovine Hs Antagonist 7.5 pKi 3
pKi 7.5 [3]
1-naphthylpiperazine Hs Antagonist 7.3 pKi 1,3
pKi 7.3 [1,3]
yohimbine Hs Antagonist 7.0 pKi 3
pKi 7.0 [3]
metergoline Hs Antagonist 6.5 pKi 1,3
pKi 6.5 [1,3]
sertindole Hs Antagonist 6.4 pKi 16
pKi 6.4 [16]
methiothepin Hs Antagonist 6.2 pKi 1,3
pKi 6.2 [1,3]
risperidone Hs Antagonist 5.9 pKi 16
pKi 5.9 [16]
methysergide Rn Antagonist 7.8 pIC50 9
pIC50 7.8 [9]
metergoline Rn Antagonist 6.3 pIC50 9
pIC50 6.3 [9]
yohimbine Rn Antagonist 6.2 pIC50 9
pIC50 6.2 [9]
View species-specific antagonist tables
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  2
Tissue Distribution
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

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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
Measurement of cAMP levels in LM(tk-) cells
Species:  Human
Tissue:  LM(tk-) cells.
Response measured:  Weak inhibition of cAMP accumulation.
References:  3
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
Phenotypes, Alleles and Disease Models 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. U.S.A., 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. British Journal of Pharmacology, 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. U.S.A., 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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