CCK-4

CCK-4
Systematic (IUPAC) name
(3S)-3-[(2S)-2-amino-3-phenylpropanamido]-3-{[(1S)-1-{[(1S)-1-carboxy -2-(indol-3-yl)ethyl]carbamoyl}-3-(methylsulfanyl)propyl]carbamoyl}propanoic acid
Clinical data
Routes of
administration		 IV
Pharmacokinetic data
Bioavailability 100%
Metabolism plasma protease enzymes
Biological half-life 13 minutes
Excretion N/A
Identifiers
CAS Number 1947-37-1 YesY
ChemSpider 27470965 N
Chemical data
Formula C29H35N5O7S
Molar mass 597.681 g/mol
 NYesY (what is this?)  (verify)

Cholecystokinin tetrapeptide (CCK-4, Trp-Met-Asp-Phe-NH2) is a peptide fragment derived from the larger peptide hormone cholecystokinin. Unlike cholecystokin which has a variety of roles in the gastrointenstinal system as well as central nervous system effects, CCK-4 acts primarily in the brain as an anxiogenic, although it does retain some GI effects, but not as much as CCK-8 or the full length polypeptide CCK-58.

CCK-4 reliably causes severe anxiety symptoms when administered to humans in a dose of as little as 50μg,[1] and is commonly used in scientific research to induce panic attacks for the purpose of testing new anxiolytic drugs.[2][3][4][5] Since it is a peptide, CCK-4 must be administered by injection, and is rapidly broken down once inside the body so has only a short duration of action,[6] although numerous synthetic analogues with modified properties are known.[7][8][9][10][11][12][13][14][15][16][17]

See also

References

  1. ↑ Daniela Eser; et al. (2005). "Panic Induction with Cholecystokinin-Tetrapeptide (CCK-4) Increases Plasma Concentrations of the Neuroactive Steroid 3α, 5α Tetrahydrodeoxycorticosterone (3α, 5α-THDOC) in Healthy Volunteers" (PDF). Neuropsychopharmacology 30 (1): 192–195. doi:10.1038/sj.npp.1300572. PMID 15467707.
  2. ↑ Bradwejn J. (July 1993). "Neurobiological investigations into the role of cholecystokinin in panic disorder". Journal of Psychiatry and Neuroscience 18 (4): 178–188. PMC 1188527. PMID 8104032.
  3. ↑ Schunck T, Erb G, Mathis A, Gilles C, Namer IJ, Hode Y, Demaziere A, Luthringer R, Macher JP. (July 2006). "Functional magnetic resonance imaging characterization of CCK-4-induced panic attack and subsequent anticipatory anxiety". NeuroImage 31 (3): 1197–1208. doi:10.1016/j.neuroimage.2006.01.035. PMID 16600640.
  4. ↑ Eser D, Schüle C, Baghai T, Floesser A, Krebs-Brown A, Enunwa M, de la Motte S, Engel R, Kucher K, Rupprecht R. (July 2007). "Evaluation of the CCK-4 model as a challenge paradigm in a population of healthy volunteers within a proof-of-concept study". Psychopharmacology 192 (4): 479–487. doi:10.1007/s00213-007-0738-7. PMID 17318504.
  5. ↑ Eser D, Leicht G, Lutz J, Wenninger S, Kirsch V, Schüle C, Karch S, Baghai T, Pogarell O, Born C, Rupprecht R, Mulert C. (December 2007). "Functional neuroanatomy of CCK-4-induced panic attacks in healthy volunteers". Human Brain Mapping 30 (2): 511–22. doi:10.1002/hbm.20522. PMID 18095276.
  6. ↑ Koulischer D, Moroder L, Deschodt-Lanckman M (August 1982). "Degradation of cholecystokinin octapeptide, related fragments and analogs by human and rat plasma in vitro". Regulatory Peptides 4 (3): 127–139. doi:10.1016/0167-0115(82)90080-5. PMID 6291099.
  7. ↑ Blommaert AG, Dhôtel H, Ducos B, Durieux C, Goudreau N, Bado A, Garbay C, Roques BP (February 1997). "Structure-based design of new constrained cyclic agonists of the cholecystokinin CCK-B receptor". Journal of Medicinal Chemistry 40 (5): 647–58. doi:10.1021/jm9603072. PMID 9057851.
  8. ↑ Bellier B, Million ME, DaNascimento S, Meudal H, Kellou S, Maigret B, Garbay C (October 2000). "Replacement of glycine with dicarbonyl and related moieties in analogues of the C-terminal pentapeptide of cholecystokinin: CCK(2) agonists displaying a novel binding mode". Journal of Medicinal Chemistry 43 (20): 3614–23. doi:10.1021/jm0000416. PMID 11020275.
  9. ↑ Léna I, Dh tel H, Garbay C, Daugé V (January 2001). "Involvement of D2 dopamine receptors in the opposing effects of two CCK-B agonists in a spatial recognition memory task: role of the anterior nucleus accumbens". Psychopharmacology 153 (2): 170–9. doi:10.1007/s002130000517. PMID 11205416.
  10. ↑ Bellier B, Garbay C (2003). "How a single inversion of configuration leads to a reversal of the binding mode: proposal of a novel arrangement of CCK2 ligands in their receptor, and contribution to the development of peptidomimetic or non-peptide CCK2 ligands". European Journal of Medicinal Chemistry 38 (7-8): 671–86. doi:10.1016/S0223-5234(03)00112-0. PMID 12932898.
  11. ↑ Bellier B, Crété D, Million ME, Beslot F, Bado A, Garbay C, Daugé V (November 2004). "New CCK2 agonists confirming the heterogeneity of CCK2 receptors: characterisation of BBL454". Naunyn-Schmiedeberg's Archives of Pharmacology 370 (5): 404–13. doi:10.1007/s00210-004-0969-7. PMID 15480577.
  12. ↑ Proskuriakova TV, Bespalova ZhD, Pal'keeva ME, Petrichenko OB, Pankratova NV, Shokhonova VA, Anokhina IP (2005). "[Biological activity of cholecystokinin-(30-33) tetrapeptide analogs]". Bioorganicheskaia Khimiia (in Russian) 31 (2): 130–9. PMID 15889786.
  13. ↑ Anokhina IP, Proskuriakova TV, Bespalova ZhD, Pal'keeva ME, Shokhonova VA, Petrichenko OB (2006). "[Effect of a cholecystokinin tetrapeptide analogue on opioid reception under acute and chronic morphine administration]". Bioorganicheskaia Khimiia (in Russian) 32 (3): 276–83. PMID 16808170.
  14. ↑ Agnes RS, Lee YS, Davis P, Ma SW, Badghisi H, Porreca F, Lai J, Hruby VJ (May 2006). "Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors". Journal of Medicinal Chemistry 49 (10): 2868–75. doi:10.1021/jm050921q. PMC 1484468. PMID 16686530.
  15. ↑ Noble F (2007). "Pharmacology of CCKRs and SAR studies of peptidic analog ligands". Current Topics in Medicinal Chemistry 7 (12): 1173–9. doi:10.2174/156802607780960447. PMID 17584139.
  16. ↑ García-López MT, González-Muñiz R, Martín-Martínez M, Herranz R (2007). "Strategies for design of non peptide CCK1R agonist/antagonist ligands". Current Topics in Medicinal Chemistry 7 (12): 1180–94. doi:10.2174/156802607780960537. PMID 17584140.
  17. ↑ Kalindjian SB, McDonald IM (2007). "Strategies for the design of non-peptide CCK2 receptor agonist and antagonist ligand". Current Topics in Medicinal Chemistry 7 (12): 1195–204. doi:10.2174/156802607780960500. PMID 17584141.
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