CCK-4

Last updated
CCK-4
Cck-4.svg
Clinical data
Other namesTetragastrin; Cholecystokinin tetrapeptide
Routes of
administration 		Intravenous
ATC code
  • None
Pharmacokinetic data
Bioavailability 100%
Metabolism Plasma protease enzymes
Elimination half-life 13 minutes
Excretion N/A
Identifiers
  • (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
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
Formula C29H35N5O7S
Molar mass 597.69 g·mol−1
3D model (JSmol)
  • CSCC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N)NC(=O)[C@H](Cc2c[nH]c3c2cccc3)N
  • InChI=1S/C29H36N6O6S/c1-42-12-11-22(33-27(39)20(30)14-18-16-32-21-10-6-5-9-19(18)21)28(40)35-24(15-25(36)37)29(41)34-23(26(31)38)13-17-7-3-2-4-8-17/h2-10,16,20,22-24,32H,11-15,30H2,1H3,(H2,31,38)(H,33,39)(H,34,41)(H,35,40)(H,36,37)/t20-,22-,23-,24-/m0/s1 X mark.svgN
  • Key:RGYLYUZOGHTBRF-BIHRQFPBSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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

References

  1. ↑ Eser D, di Michele F, Zwanzger P, Pasini A, Baghai TC, Schüle C, et al. (January 2005). "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. 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 & Neuroscience. 18 (4): 178–88. PMC   1188527 . PMID   8104032.
  3. ↑ Schunck T, Erb G, Mathis A, Gilles C, Namer IJ, Hode Y, et al. (July 2006). "Functional magnetic resonance imaging characterization of CCK-4-induced panic attack and subsequent anticipatory anxiety". NeuroImage. 31 (3): 1197–208. doi:10.1016/j.neuroimage.2006.01.035. PMID   16600640. S2CID   2430104.
  4. ↑ Eser D, Schüle C, Baghai T, Floesser A, Krebs-Brown A, Enunwa M, et al. (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): 479–87. doi:10.1007/s00213-007-0738-7. PMID   17318504. S2CID   21457632.
  5. ↑ Eser D, Leicht G, Lutz J, Wenninger S, Kirsch V, Schüle C, et al. (February 2009). "Functional neuroanatomy of CCK-4-induced panic attacks in healthy volunteers". Human Brain Mapping. 30 (2): 511–22. doi:10.1002/hbm.20522. PMC   6870703 . 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): 127–39. doi:10.1016/0167-0115(82)90080-5. PMID   6291099. S2CID   20585962.
  7. ↑ Blommaert AG, Dhôtel H, Ducos B, Durieux C, Goudreau N, Bado A, et al. (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. S2CID   39490703.
  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. S2CID   20603424.
  12. ↑ Proskuriakova TV, Bespalova Z, 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 Z, 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. doi:10.1134/s106816200603006x. PMID   16808170. S2CID   23993886.
  14. ↑ Agnes RS, Lee YS, Davis P, Ma SW, Badghisi H, Porreca F, et al. (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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