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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