CCK-4 explained

Cholecystokinin tetrapeptide (CCK-4, tetragastrin, 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 gastrointestinal 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 50 μg,^[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

• Pentagastrin

Notes and References

1. Eser D, di Michele F, Zwanzger P, Pasini A, Baghai TC, Schüle C, Rupprecht R, Romeo E . 6 . Panic induction with cholecystokinin-tetrapeptide (CCK-4) Increases plasma concentrations of the neuroactive steroid 3alpha, 5alpha tetrahydrodeoxycorticosterone (3alpha, 5alpha-THDOC) in healthy volunteers . Neuropsychopharmacology . 30 . 1 . 192–5 . January 2005 . 15467707 . 10.1038/sj.npp.1300572 . free .
2. Bradwejn J . Neurobiological investigations into the role of cholecystokinin in panic disorder . Journal of Psychiatry & Neuroscience . 18 . 4 . 178–88 . July 1993 . 8104032 . 1188527 .
3. Schunck T, Erb G, Mathis A, Gilles C, Namer IJ, Hode Y, Demaziere A, Luthringer R, Macher JP . 6 . Functional magnetic resonance imaging characterization of CCK-4-induced panic attack and subsequent anticipatory anxiety . NeuroImage . 31 . 3 . 1197–208 . July 2006 . 16600640 . 10.1016/j.neuroimage.2006.01.035 . 2430104 .
4. Eser D, Schüle C, Baghai T, Floesser A, Krebs-Brown A, Enunwa M, de la Motte S, Engel R, Kucher K, Rupprecht R . 6 . 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 . 479–87 . July 2007 . 17318504 . 10.1007/s00213-007-0738-7 . 21457632 .
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 . 6 . Functional neuroanatomy of CCK-4-induced panic attacks in healthy volunteers . Human Brain Mapping . 30 . 2 . 511–22 . February 2009 . 18095276 . 6870703 . 10.1002/hbm.20522 .
6. Koulischer D, Moroder L, Deschodt-Lanckman M . Degradation of cholecystokinin octapeptide, related fragments and analogs by human and rat plasma in vitro . Regulatory Peptides . 4 . 3 . 127–39 . August 1982 . 6291099 . 10.1016/0167-0115(82)90080-5 . 20585962 .
7. Blommaert AG, Dhôtel H, Ducos B, Durieux C, Goudreau N, Bado A, Garbay C, Roques BP . 6 . Structure-based design of new constrained cyclic agonists of the cholecystokinin CCK-B receptor . Journal of Medicinal Chemistry . 40 . 5 . 647–58 . February 1997 . 9057851 . 10.1021/jm9603072 .
8. Bellier B, Million ME, DaNascimento S, Meudal H, Kellou S, Maigret B, Garbay C . 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 . October 2000 . 11020275 . 10.1021/jm0000416 .
9. Léna I, Dh tel H, Garbay C, Daugé V . 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 . January 2001 . 11205416 . 10.1007/s002130000517 . 39490703 .
10. Bellier B, Garbay C . 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 . 2003 . 12932898 . 10.1016/S0223-5234(03)00112-0 .
11. Bellier B, Crété D, Million ME, Beslot F, Bado A, Garbay C, Daugé V . New CCK2 agonists confirming the heterogeneity of CCK2 receptors: characterisation of BBL454 . Naunyn-Schmiedeberg's Archives of Pharmacology . 370 . 5 . 404–13 . November 2004 . 15480577 . 10.1007/s00210-004-0969-7 . 20603424 .
12. Proskuriakova TV, Bespalova Z, Pal'keeva ME, Petrichenko OB, Pankratova NV, Shokhonova VA, Anokhina IP . [Biological activity of cholecystokinin-(30-33) tetrapeptide analogs] . ru . Bioorganicheskaia Khimiia . 31 . 2 . 130–9 . 2005 . 15889786 .
13. Anokhina IP, Proskuriakova TV, Bespalova Z, Pal'keeva ME, Shokhonova VA, Petrichenko OB . [Effect of a cholecystokinin tetrapeptide analogue on opioid reception under acute and chronic morphine administration] . ru . Bioorganicheskaia Khimiia . 32 . 3 . 276–83 . 2006 . 16808170 . 10.1134/s106816200603006x . 23993886 .
14. Agnes RS, Lee YS, Davis P, Ma SW, Badghisi H, Porreca F, Lai J, Hruby VJ . 6 . Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors . Journal of Medicinal Chemistry . 49 . 10 . 2868–75 . May 2006 . 16686530 . 1484468 . 10.1021/jm050921q .
15. Noble F . Pharmacology of CCKRs and SAR studies of peptidic analog ligands . Current Topics in Medicinal Chemistry . 7 . 12 . 1173–9 . 2007 . 17584139 . 10.2174/156802607780960447 .
16. García-López MT, González-Muñiz R, Martín-Martínez M, Herranz R . Strategies for design of non peptide CCK1R agonist/antagonist ligands . Current Topics in Medicinal Chemistry . 7 . 12 . 1180–94 . 2007 . 17584140 . 10.2174/156802607780960537 .
17. Kalindjian SB, McDonald IM . Strategies for the design of non-peptide CCK2 receptor agonist and antagonist ligand . Current Topics in Medicinal Chemistry . 7 . 12 . 1195–204 . 2007 . 17584141 . 10.2174/156802607780960500 .