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Cholecystokinin tetrapeptide (CCK-4, Trp-Met-Asp-Phe-NH2; also PTK7) 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 alsoEdit

ReferencesEdit

  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. Neuropsychopharmacology 30 (1): 192–195.
  2. Bradwejn J. (July 1993). Neurobiological investigations into the role of cholecystokinin in panic disorder. Journal of Psychiatry and Neuroscience 18 (4): 178–188.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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 31 (2): 130–9.
  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 32 (3): 276–83.
  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.
  15. Noble F (2007). Pharmacology of CCKRs and SAR studies of peptidic analog ligands. Current Topics in Medicinal Chemistry 7 (12): 1173–9.
  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.
  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.


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