| Revision as of 04:54, 31 May 2011 editDcirovic (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers, Rollbackers253,275 editsNo edit summary← Previous edit |
Latest revision as of 22:43, 2 February 2023 edit undoDeliciousBoson (talk | contribs)69 edits Describe primary property of compound as an anxiogenicTag: Visual edit |
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{{Short description|Anxiogenic agent}} |
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{{Drugbox |
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{{Drugbox |
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| Verifiedfields = changed |
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| IUPAC_name = (3''S'')-3--3-{carbamoyl}-3-(methylsulfanyl)propyl]carbamoyl}propanoic acid |
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| Watchedfields = changed |
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| image = CCK-4.png |
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| verifiedrevid = 431772029 |
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| width = 240 |
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| IUPAC_name = (3''S'')-3--3-<nowiki/>{carbamoyl}-3-(methylsulfanyl)propyl]carbamoyl}propanoic acid |
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| CAS_number = 1947-37-1 |
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| image = Cck-4.svg |
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| ATC_prefix = |
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| width = 240 |
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| ATC_suffix = |
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| PubChem = |
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<!--Clinical data--> |
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| DrugBank = |
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| tradename = |
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| C=29|H=35|N=5|O=7|S=1 |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| molecular_weight = 597.681 g/mol |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| smiles = c3cccc1c3ncc1CC(C(=O)O)NC(=O)C(CCSC)NC(=O)C(CC(O)=O)NC(=O)C(N)Cc2ccccc2 |
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| pregnancy_category = |
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| bioavailability = 100% |
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> |
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| protein_bound = |
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| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| metabolism = plasma protease enzymes |
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| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> |
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| elimination_half-life = 13 minutes |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| excretion = N/A |
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| legal_status = |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_category= |
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> |
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| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_status = |
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| routes_of_administration = IV |
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| routes_of_administration = IV |
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<!--Pharmacokinetic data--> |
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| bioavailability = 100% |
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| protein_bound = |
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| metabolism = plasma protease enzymes |
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| elimination_half-life = 13 minutes |
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| excretion = N/A |
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<!--Identifiers--> |
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| synonyms = Tetragastrin; Cholecystokinin tetrapeptide |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 1947-37-1 |
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| ATC_prefix = |
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| ATC_suffix = |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 0OL293AV80 |
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| PubChem = 446569 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 393888 |
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| ChEBI = 137728 |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 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 |
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| StdInChIKey = RGYLYUZOGHTBRF-BIHRQFPBSA-N |
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<!--Chemical data--> |
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| C=29 | H=35 | N=5 | O=7 | S=1 |
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| smiles = CSCC(C(=O)N(CC(=O)O)C(=O)N(Cc1ccccc1)C(=O)N)NC(=O)(Cc2cc3c2cccc3)N |
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}} |
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}} |
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'''Cholecystokinin tetrapeptide''' ('''CCK-4''', ''']-]-]-]-NH<sub>2</sub>'''; also '''PTK7''') is a ] fragment derived from the larger peptide hormone ]. Unlike cholecystokin which has a variety of roles in the gastrointenstinal system as well as ] effects, CCK-4 acts primarily in the brain as an ], although it does retain some GI effects, but not as much as CCK-8 or the full length polypeptide CCK-58. |
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'''Cholecystokinin tetrapeptide''' ('''CCK-4''', '''tetragastrin''', ''']-]-]-]-NH<sub>2</sub>''') is a ] fragment derived from the larger peptide hormone ]. Unlike cholecystokin which has a variety of roles in the gastrointestinal system as well as ] effects, CCK-4 acts primarily in the brain as an ], although it does retain some GI effects, but not as much as CCK-8 or the full length polypeptide CCK-58. |
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CCK-4 reliably causes severe ] symptoms when administered to humans in a dose of as little as 50 μg,<ref>{{cite journal | vauthors = Eser D, di Michele F, Zwanzger P, Pasini A, Baghai TC, Schüle C, Rupprecht R, Romeo E | display-authors = 6 | title = Panic induction with cholecystokinin-tetrapeptide (CCK-4) Increases plasma concentrations of the neuroactive steroid 3alpha, 5alpha tetrahydrodeoxycorticosterone (3alpha, 5alpha-THDOC) in healthy volunteers | journal = Neuropsychopharmacology | volume = 30 | issue = 1 | pages = 192–5 | date = January 2005 | pmid = 15467707 | doi = 10.1038/sj.npp.1300572 | doi-access = free }}</ref> |
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CCK-4 reliably causes severe ] symptoms when administered to humans in a dose of as little as 50μg,<ref>{{Cite journal |
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and is commonly used in scientific research to induce ]s for the purpose of testing new ] drugs.<ref>{{cite journal | vauthors = Bradwejn J | title = Neurobiological investigations into the role of cholecystokinin in panic disorder | journal = Journal of Psychiatry & Neuroscience | volume = 18 | issue = 4 | pages = 178–88 | date = July 1993 | pmid = 8104032 | pmc = 1188527 }}</ref><ref>{{cite journal | vauthors = Schunck T, Erb G, Mathis A, Gilles C, Namer IJ, Hode Y, Demaziere A, Luthringer R, Macher JP | display-authors = 6 | title = Functional magnetic resonance imaging characterization of CCK-4-induced panic attack and subsequent anticipatory anxiety | journal = NeuroImage | volume = 31 | issue = 3 | pages = 1197–208 | date = July 2006 | pmid = 16600640 | doi = 10.1016/j.neuroimage.2006.01.035 | s2cid = 2430104 }}</ref><ref>{{cite journal | vauthors = Eser D, Schüle C, Baghai T, Floesser A, Krebs-Brown A, Enunwa M, de la Motte S, Engel R, Kucher K, Rupprecht R | display-authors = 6 | title = Evaluation of the CCK-4 model as a challenge paradigm in a population of healthy volunteers within a proof-of-concept study | journal = Psychopharmacology | volume = 192 | issue = 4 | pages = 479–87 | date = July 2007 | pmid = 17318504 | doi = 10.1007/s00213-007-0738-7 | s2cid = 21457632 }}</ref><ref>{{cite journal | vauthors = Eser D, Leicht G, Lutz J, Wenninger S, Kirsch V, Schüle C, Karch S, Baghai T, Pogarell O, Born C, Rupprecht R, Mulert C | display-authors = 6 | title = Functional neuroanatomy of CCK-4-induced panic attacks in healthy volunteers | journal = Human Brain Mapping | volume = 30 | issue = 2 | pages = 511–22 | date = February 2009 | pmid = 18095276 | pmc = 6870703 | doi = 10.1002/hbm.20522 }}</ref> |
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| author = Daniela Eser et al. |
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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,<ref>{{cite journal | vauthors = Koulischer D, Moroder L, Deschodt-Lanckman M | title = Degradation of cholecystokinin octapeptide, related fragments and analogs by human and rat plasma in vitro | journal = Regulatory Peptides | volume = 4 | issue = 3 | pages = 127–39 | date = August 1982 | pmid = 6291099 | doi = 10.1016/0167-0115(82)90080-5 | s2cid = 20585962 }}</ref> although numerous synthetic analogues with modified properties are known.<ref name="pmid9057851">{{cite journal | vauthors = Blommaert AG, Dhôtel H, Ducos B, Durieux C, Goudreau N, Bado A, Garbay C, Roques BP | display-authors = 6 | title = Structure-based design of new constrained cyclic agonists of the cholecystokinin CCK-B receptor | journal = Journal of Medicinal Chemistry | volume = 40 | issue = 5 | pages = 647–58 | date = February 1997 | pmid = 9057851 | doi = 10.1021/jm9603072 }}</ref><ref name="pmid11020275">{{cite journal | vauthors = Bellier B, Million ME, DaNascimento S, Meudal H, Kellou S, Maigret B, Garbay C | title = 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 = Journal of Medicinal Chemistry | volume = 43 | issue = 20 | pages = 3614–23 | date = October 2000 | pmid = 11020275 | doi = 10.1021/jm0000416 }}</ref><ref name="pmid11205416">{{cite journal | vauthors = Léna I, Dh tel H, Garbay C, Daugé V | title = 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 | journal = Psychopharmacology | volume = 153 | issue = 2 | pages = 170–9 | date = January 2001 | pmid = 11205416 | doi = 10.1007/s002130000517 | s2cid = 39490703 }}</ref><ref name="pmid12932898">{{cite journal | vauthors = Bellier B, Garbay C | title = 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 | journal = European Journal of Medicinal Chemistry | volume = 38 | issue = 7–8 | pages = 671–86 | year = 2003 | pmid = 12932898 | doi = 10.1016/S0223-5234(03)00112-0 }}</ref><ref name="pmid15480577">{{cite journal | vauthors = Bellier B, Crété D, Million ME, Beslot F, Bado A, Garbay C, Daugé V | title = New CCK2 agonists confirming the heterogeneity of CCK2 receptors: characterisation of BBL454 | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 370 | issue = 5 | pages = 404–13 | date = November 2004 | pmid = 15480577 | doi = 10.1007/s00210-004-0969-7 | s2cid = 20603424 }}</ref><ref name="pmid15889786">{{cite journal | vauthors = Proskuriakova TV, Bespalova Z, Pal'keeva ME, Petrichenko OB, Pankratova NV, Shokhonova VA, Anokhina IP | title = | language = ru | journal = Bioorganicheskaia Khimiia | volume = 31 | issue = 2 | pages = 130–9 | year = 2005 | pmid = 15889786 }}</ref><ref name="pmid16808170">{{cite journal | vauthors = Anokhina IP, Proskuriakova TV, Bespalova Z, Pal'keeva ME, Shokhonova VA, Petrichenko OB | title = | language = ru | journal = Bioorganicheskaia Khimiia | volume = 32 | issue = 3 | pages = 276–83 | year = 2006 | pmid = 16808170 | doi = 10.1134/s106816200603006x | s2cid = 23993886 }}</ref><ref name="pmid16686530">{{cite journal | vauthors = Agnes RS, Lee YS, Davis P, Ma SW, Badghisi H, Porreca F, Lai J, Hruby VJ | display-authors = 6 | title = Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors | journal = Journal of Medicinal Chemistry | volume = 49 | issue = 10 | pages = 2868–75 | date = May 2006 | pmid = 16686530 | pmc = 1484468 | doi = 10.1021/jm050921q }}</ref><ref name="pmid17584139">{{cite journal | vauthors = Noble F | title = Pharmacology of CCKRs and SAR studies of peptidic analog ligands | journal = Current Topics in Medicinal Chemistry | volume = 7 | issue = 12 | pages = 1173–9 | year = 2007 | pmid = 17584139 | doi = 10.2174/156802607780960447 }}</ref><ref name="pmid17584140">{{cite journal | vauthors = García-López MT, González-Muñiz R, Martín-Martínez M, Herranz R | title = Strategies for design of non peptide CCK1R agonist/antagonist ligands | journal = Current Topics in Medicinal Chemistry | volume = 7 | issue = 12 | pages = 1180–94 | year = 2007 | pmid = 17584140 | doi = 10.2174/156802607780960537 }}</ref><ref name="pmid17584141">{{cite journal | vauthors = Kalindjian SB, McDonald IM | title = Strategies for the design of non-peptide CCK2 receptor agonist and antagonist ligand | journal = Current Topics in Medicinal Chemistry | volume = 7 | issue = 12 | pages = 1195–204 | year = 2007 | pmid = 17584141 | doi = 10.2174/156802607780960500 }}</ref> |
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| title = Panic Induction with Cholecystokinin-Tetrapeptide (CCK-4) Increases Plasma Concentrations of the Neuroactive Steroid 3α, 5α Tetrahydrodeoxycorticosterone (3α, 5α-THDOC) in Healthy Volunteers |
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| url = http://www.nature.com/npp/journal/v30/n1/pdf/1300572a.pdf |
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| journal = ] |
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| year = 2005 |
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| volume = 30 |
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| pages = 192–195 |
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| doi = 10.1038/sj.npp.1300572 |
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| pmid = 15467707 |
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| issue = 1 |
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}}</ref> |
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and is commonly used in scientific research to induce ]s for the purpose of testing new ] drugs.<ref>{{Cite journal |
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| author = Bradwejn J. |
|
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| title = Neurobiological investigations into the role of cholecystokinin in panic disorder |
|
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| journal = ] |
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| year = 1993 |
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| month = July |
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| volume = 18 |
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| issue = 4 |
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| pages = 178–188 |
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| pmid = 8104032 |
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| pmc = 1188527 |
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}}</ref><ref>{{Cite journal |
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| author = Schunck T, Erb G, Mathis A, Gilles C, Namer IJ, Hode Y, Demaziere A, Luthringer R, Macher JP. |
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| title = Functional magnetic resonance imaging characterization of CCK-4-induced panic attack and subsequent anticipatory anxiety |
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| journal = ] |
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| year = 2006 |
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| month = July |
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| volume = 31 |
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| issue = 3 |
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| pages = 1197–1208 |
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| pmid = 16600640 |
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| doi = 10.1016/j.neuroimage.2006.01.035 |
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}}</ref><ref>{{Cite journal |
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| author = Eser D, Schüle C, Baghai T, Floesser A, Krebs-Brown A, Enunwa M, de la Motte S, Engel R, Kucher K, Rupprecht R. |
|
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| title = Evaluation of the CCK-4 model as a challenge paradigm in a population of healthy volunteers within a proof-of-concept study |
|
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| journal = ] |
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| year = 2007 |
|
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| month = July |
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| volume = 192 |
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| issue = 4 |
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| pages = 479–487 |
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| pmid = 17318504 |
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| doi = 10.1007/s00213-007-0738-7 |
|
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}}</ref><ref>{{Cite journal |
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| author = Eser D, Leicht G, Lutz J, Wenninger S, Kirsch V, Schüle C, Karch S, Baghai T, Pogarell O, Born C, Rupprecht R, Mulert C. |
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| title = Functional neuroanatomy of CCK-4-induced panic attacks in healthy volunteers |
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| journal = ] |
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| year = 2007 |
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| month = December |
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| pmid = 18095276 |
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| volume = 30 |
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| issue = 2 |
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| pages = 511–22 |
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| doi = 10.1002/hbm.20522 |
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}}</ref> |
|
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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,<ref>{{Cite journal |
|
|
| author = Koulischer D, Moroder L, Deschodt-Lanckman M |
|
|
| title = Degradation of cholecystokinin octapeptide, related fragments and analogs by human and rat plasma in vitro |
|
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| journal = ] |
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| year = 1982 |
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| month = August |
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| volume = 4 |
|
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| issue = 3 |
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| pages = 127–139 |
|
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| pmid = 6291099 |
|
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| doi = 10.1016/0167-0115(82)90080-5 |
|
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}}</ref> although numerous synthetic analogues with modified properties are known.<ref name="pmid9057851">{{cite journal |author=Blommaert AG, Dhôtel H, Ducos B, Durieux C, Goudreau N, Bado A, Garbay C, Roques BP |title=Structure-based design of new constrained cyclic agonists of the cholecystokinin CCK-B receptor |journal=Journal of Medicinal Chemistry |volume=40 |issue=5 |pages=647–58 |year=1997 |month=February |pmid=9057851 |doi=10.1021/jm9603072 |url=}}</ref><ref name="pmid11020275">{{cite journal |author=Bellier B, Million ME, DaNascimento S, Meudal H, Kellou S, Maigret B, Garbay C |title=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=Journal of Medicinal Chemistry |volume=43 |issue=20 |pages=3614–23 |year=2000 |month=October |pmid=11020275 |doi= 10.1021/jm0000416|url=}}</ref><ref name="pmid11205416">{{cite journal |author=Léna I, Dh tel H, Garbay C, Daugé V |title=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 |journal=Psychopharmacology |volume=153 |issue=2 |pages=170–9 |year=2001 |month=January |pmid=11205416 |doi= 10.1007/s002130000517|url=}}</ref><ref name="pmid12932898">{{cite journal |author=Bellier B, Garbay C |title=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 |journal=European Journal of Medicinal Chemistry |volume=38 |issue=7-8 |pages=671–86 |year=2003 |pmid=12932898 |doi= 10.1016/S0223-5234(03)00112-0|url=}}</ref><ref name="pmid15480577">{{cite journal |author=Bellier B, Crété D, Million ME, Beslot F, Bado A, Garbay C, Daugé V |title=New CCK2 agonists confirming the heterogeneity of CCK2 receptors: characterisation of BBL454 |journal=Naunyn-Schmiedeberg's Archives of Pharmacology |volume=370 |issue=5 |pages=404–13 |year=2004 |month=November |pmid=15480577 |doi=10.1007/s00210-004-0969-7 |url=}}</ref><ref name="pmid15889786">{{cite journal |author=Proskuriakova TV, Bespalova ZhD, Pal'keeva ME, Petrichenko OB, Pankratova NV, Shokhonova VA, Anokhina IP |title= |language=Russian |journal=Bioorganicheskaia Khimiia |volume=31 |issue=2 |pages=130–9 |year=2005 |pmid=15889786 |doi= |url=}}</ref><ref name="pmid16808170">{{cite journal |author=Anokhina IP, Proskuriakova TV, Bespalova ZhD, Pal'keeva ME, Shokhonova VA, Petrichenko OB |title= |language=Russian |journal=Bioorganicheskaia Khimiia |volume=32 |issue=3 |pages=276–83 |year=2006 |pmid=16808170 |doi= |url=}}</ref><ref name="pmid16686530">{{cite journal |author=Agnes RS, Lee YS, Davis P, Ma SW, Badghisi H, Porreca F, Lai J, Hruby VJ |title=Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors |journal=Journal of Medicinal Chemistry |volume=49 |issue=10 |pages=2868–75 |year=2006 |month=May |pmid=16686530 |pmc=1484468 |doi=10.1021/jm050921q |url=}}</ref><ref name="pmid17584139">{{cite journal |author=Noble F |title=Pharmacology of CCKRs and SAR studies of peptidic analog ligands |journal=Current Topics in Medicinal Chemistry |volume=7 |issue=12 |pages=1173–9 |year=2007 |pmid=17584139 |doi= 10.2174/156802607780960447|url=}}</ref><ref name="pmid17584140">{{cite journal |author=García-López MT, González-Muñiz R, Martín-Martínez M, Herranz R |title=Strategies for design of non peptide CCK1R agonist/antagonist ligands |journal=Current Topics in Medicinal Chemistry |volume=7 |issue=12 |pages=1180–94 |year=2007 |pmid=17584140 |doi= 10.2174/156802607780960537|url=}}</ref><ref name="pmid17584141">{{cite journal |author=Kalindjian SB, McDonald IM |title=Strategies for the design of non-peptide CCK2 receptor agonist and antagonist ligand |journal=Current Topics in Medicinal Chemistry |volume=7 |issue=12 |pages=1195–204 |year=2007 |pmid=17584141 |doi= 10.2174/156802607780960500|url=}}</ref> |
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==See also== |
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== See also == |
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==References== |
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== References == |
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{{Reflist}} |
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{{Neuropeptide agonists and antagonists}} |
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{{pharma-stub}} |
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