Tachykinin receptor 1

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Tachykinin receptor 1
External IDsOMIM162323 MGI98475 HomoloGene20288 IUPHAR: NK1 GeneCards: TACR1 Gene
RNA expression pattern
More reference expression data
RefSeq (mRNA)NM_001058NM_009313
RefSeq (protein)NP_001049NP_033339
Location (UCSC)Chr 2:
75.13 - 75.28 Mb
Chr 6:
82.37 - 82.53 Mb
PubMed search[1][2]

The tachykinin receptor 1 (TACR1) also known as neurokinin 1 receptor (NK1R) or substance P receptor (SPR) is a G protein coupled receptor found in the central nervous system and peripheral nervous system. The endogenous ligand for this receptor is Substance P, although it has some affinity for other tachykinins. The protein is the product of the TACR1 gene.[1]

Clinical significance

This receptor is considered an attractive drug target, particularly with regards to potential analgesics and anti-depressants.[2][3] It was identified as a candidate in the etiology of bipolar disorder by a 2008 study.[4] Furthermore TACR1 antagonists have shown promise for the treatment in alcoholism.[5] Finally TACR1 antagonists may also have a role as novel antiemetics.[6]

Selective ligands

Many selective ligands for NK1 are now available, several of which have gone into clinical use as antiemetics.


  • GR-73632 - potent and selective agonist, EC50 2nM, 5-amino acid polypeptide chain. CAS# 133156-06-6


  • Aprepitant
  • Casopitant
  • Ezlopitant
  • Fosaprepitant
  • Lanepitant
  • Maropitant
  • Vestipitant
  • L-733,060
  • L-741,671
  • L-742,694
  • RP-67580 - potent and selective antagonist, Ki 2.9nM, (3aR,7aR)-Octahydro-2-[1-imino-2-(2-methoxyphenyl)ethyl ]-7,7-diphenyl-4H-isoindol, CAS# 135911-02-3
  • RPR-100,893
  • CP-96345
  • CP-99994
  • GR-205,171
  • TAK-637
  • T-2328

See also


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Further reading

  • Burcher E (1989). "The study of tachykinin receptors". Clin. Exp. Pharmacol. Physiol. 16 (6): 539–43. doi:10.1111/j.1440-1681.1989.tb01602.x. PMID 2548782. 
  • Kowall NW, Quigley BJ, Krause JE; et al. (1993). "Substance P and substance P receptor histochemistry in human neurodegenerative diseases". Regul. Pept. 46 (1-2): 174–85. doi:10.1016/0167-0115(93)90028-7. PMID 7692486. 
  • Patacchini R, Maggi CA (2002). "Peripheral tachykinin receptors as targets for new drugs". Eur. J. Pharmacol. 429 (1-3): 13–21. doi:10.1016/S0014-2999(01)01301-2. PMID 11698023. 
  • Saito R, Takano Y, Kamiya HO (2003). "Roles of substance P and NK(1) receptor in the brainstem in the development of emesis". J. Pharmacol. Sci. 91 (2): 87–94. doi:10.1254/jphs.91.87. PMID 12686752. 
  • Fong TM, Yu H, Huang RR, Strader CD (1992). "The extracellular domain of the neurokinin-1 receptor is required for high-affinity binding of peptides". Biochemistry. 31 (47): 11806–11. doi:10.1021/bi00162a019. PMID 1280161. 
  • Fong TM, Huang RR, Strader CD (1993). "Localization of agonist and antagonist binding domains of the human neurokinin-1 receptor". J. Biol. Chem. 267 (36): 25664–7. PMID 1281469. 
  • Fong TM, Anderson SA, Yu H; et al. (1992). "Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor". Mol. Pharmacol. 41 (1): 24–30. PMID 1310144. 
  • Takahashi K, Tanaka A, Hara M, Nakanishi S (1992). "The primary structure and gene organization of human substance P and neuromedin K receptors". Eur. J. Biochem. 204 (3): 1025–33. doi:10.1111/j.1432-1033.1992.tb16724.x. PMID 1312928. 
  • Walsh DA, Mapp PI, Wharton J; et al. (1992). "Localisation and characterisation of substance P binding to human synovial tissue in rheumatoid arthritis". Ann. Rheum. Dis. 51 (3): 313–7. doi:10.1136/ard.51.3.313. PMC 1004650Freely accessible. PMID 1374227. 
  • Gerard NP, Garraway LA, Eddy RL; et al. (1991). "Human substance P receptor (NK-1): organization of the gene, chromosome localization, and functional expression of cDNA clones". Biochemistry. 30 (44): 10640–6. doi:10.1021/bi00108a006. PMID 1657150. 
  • Hopkins B, Powell SJ, Danks P; et al. (1991). "Isolation and characterisation of the human lung NK-1 receptor cDNA". Biochem. Biophys. Res. Commun. 180 (2): 1110–7. doi:10.1016/S0006-291X(05)81181-7. PMID 1659396. 
  • Takeda Y, Chou KB, Takeda J; et al. (1991). "Molecular cloning, structural characterization and functional expression of the human substance P receptor". Biochem. Biophys. Res. Commun. 179 (3): 1232–40. doi:10.1016/0006-291X(91)91704-G. PMID 1718267. 
  • Giuliani S, Barbanti G, Turini D; et al. (1992). "NK2 tachykinin receptors and contraction of circular muscle of the human colon: characterization of the NK2 receptor subtype". Eur. J. Pharmacol. 203 (3): 365–70. doi:10.1016/0014-2999(91)90892-T. PMID 1723045. 
  • Ichinose H, Katoh S, Sueoka T; et al. (1991). "Cloning and sequencing of cDNA encoding human sepiapterin reductase--an enzyme involved in tetrahydrobiopterin biosynthesis". Biochem. Biophys. Res. Commun. 179 (1): 183–9. doi:10.1016/0006-291X(91)91352-D. PMID 1883349. 
  • Thöny B, Heizmann CW, Mattei MG (1995). "Human GTP-cyclohydrolase I gene and sepiapterin reductase gene map to region 14q21-q22 and 2p14-p12, respectively, by in situ hybridization". Genomics. 26 (1): 168–70. doi:10.1016/0888-7543(95)80101-Q. PMID 7782081. 
  • Fong TM, Cascieri MA, Yu H; et al. (1993). "Amino-aromatic interaction between histidine 197 of the neurokinin-1 receptor and CP 96345". Nature. 362 (6418): 350–3. doi:10.1038/362350a0. PMID 8384323. 
  • Derocq JM, Ségui M, Blazy C; et al. (1997). "Effect of substance P on cytokine production by human astrocytic cells and blood mononuclear cells: characterization of novel tachykinin receptor antagonists". FEBS Lett. 399 (3): 321–5. doi:10.1016/S0014-5793(96)01346-4. PMID 8985172. 
  • De Felipe C, Herrero JF, O'Brien JA; et al. (1998). "Altered nociception, analgesia and aggression in mice lacking the receptor for substance P". Nature. 392 (6674): 394–7. doi:10.1038/32904. PMID 9537323. 

External links

  1. Takeda Y, Chou KB, Takeda J, Sachais BS, Krause JE (1991). "Molecular cloning, structural characterization and functional expression of the human substance P receptor". Biochem. Biophys. Res. Commun. 179 (3): 1232–40. doi:10.1016/0006-291X(91)91704-G. PMID 1718267. 
  2. Humphrey JM (2003). "Medicinal chemistry of selective neurokinin-1 antagonists". Current topics in medicinal chemistry. 3 (12): 1423–35. doi:10.2174/1568026033451925. PMID 12871173. 
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  6. Jordan K (2006). "Neurokinin-1-receptor antagonists: a new approach in antiemetic therapy". Onkologie. 29 (1-2): 39–43. doi:10.1159/000089800. PMID 16514255.