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CI-988

Izvor: Wikipedija
CI-988
(IUPAC) ime
4-([(1R)-2-([(2R)-3-(1H-indol-3-yl)-2-methyl-1-oxo-2-([(tricyclo[3.3.1.13,7]dec-2-yloxy) carbonyl]amino)propyl]amino)-1-phenylethyl]amino)-4-oxobutanoic acid
Klinički podaci
Identifikatori
CAS broj130332-27-3
ATC kod?
PubChem[1][2]108186
Hemijski podaci
FormulaC35H42N4O6 
Mol. masa614.73 g/mol
SMILESeMolekuli &PubHem
InChI
InChI=1S/C35H42N4O6.C7H17NO5/c1-35(18-26-19-36-28-10-6-5-9-27(26)28,39-34(44)45-32-24-14-21-13-22(16-24)17-25(32)15-21)33(43)37-20-29(23-7-3-2-4-8-23)38-30(40)11-12-31(41)42;1-8-2-4(10)6(12)7(13)5(11)3-9/h2-10,19,21-22,24-25,29,32,36H,11-18,20H2,1H3,(H,37,43)(H,38,40)(H,39,44)(H,41,42);4-13H,2-3H2,1H3/t21?,22?,24?,25?,29-,32?,35+;4-,5+,6+,7+/m00/s1 DaY
Key: DEZUAGYSLSZLFO-DRGCLBCYSA-N DaY
Farmakoinformacioni podaci
Trudnoća?
Pravni status

CI-988 (PD-134,308) je lek koji deluje kaoholecistokininski antagonist, selektivan zaCCKB tip. U životinjskim studijama on je manifestovaoanksiolitsko dejstvo[3][4] kao i pojačanjeanalgetskog dejstvamorfina[5] i endogenih opioidnih peptida,[6][7] sprečavanje razvoja tolerancije na opioide[8][9] i umanjenje simptoma povlačenja.[10][11] Konsekventno smatralo se da on možda može da nađe kliničku primenu u lečenju bola i anksioznosti kod ljudi, ali su rezultati kliničkih ispitivanja bili razočaravajući. Samo su minimalni terapeutski efekti primećeni čak i na visokim dozama.[12][13][14][15] Razlozi za neuspeh CI-988-a i drugih CCKB antagonista na ljudima uprkos pozitivnih rezultata na životinjama nisu jasni. Slabe farmakokinetičke osobine su moguće objašnjenje,[16] tako da se CCKB antagonisti još uvek istražuju kao mogući pomoćni lekovi za pojačanje dejstva drugih lekova.[17]

Reference

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  1. ↑Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519.  edit
  2. ↑Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1. 
  3. ↑Hughes J, Boden P, Costall B, Domeney A, Kelly E, Horwell DC, Hunter JC, Pinnock RD, Woodruff GN. Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity.Proceedings of the National Academy of Sciences USA. 1990 Sep;87(17):6728-32.PMID 1975695
  4. ↑Singh L, Field MJ, Hughes J, Menzies R, Oles RJ, Vass CA, Woodruff GN. The behavioural properties of CI-988, a selective cholecystokininB receptor antagonist.British Journal of Pharmacology. 1991 Sep;104(1):239-45.PMID 1686205
  5. ↑Wiesenfeld-Hallin Z, Xu XJ, Hughes J, Horwell DC, Hökfelt T. PD134308, a selective antagonist of cholecystokinin type B receptor, enhances the analgesic effect of morphine and synergistically interacts with intrathecal galanin to depress spinal nociceptive reflexes.Proceedings of the National Academy of Sciences USA. 1990 Sep;87(18):7105-9.PMID 1698290
  6. ↑Durieux C, Derrien M, Maldonado R, Valverde O, Blommaert A, Fournié-Zaluski MC, Roques BP. CCK-B antagonists exhibit antidepressant-like effects and potentiate endogenous enkephalin analgesia. Correlation with in vivo binding affinities and brain penetration.Annals of the New York Academy of Sciences. 1994 Mar 23;713:355-7.PMID 8185186
  7. ↑Valverde O, Maldonado R, Fournie-Zaluski MC, Roques BP. Cholecystokinin B antagonists strongly potentiate antinociception mediated by endogenous enkephalins.Journal of Pharmacology and Experimental Therapeutics. 1994 Jul;270(1):77-88.PMID 8035345
  8. ↑Xu XJ, Wiesenfeld-Hallin Z, Hughes J, Horwell DC, Hökfelt T. CI988, a selective antagonist of cholecystokininB receptors, prevents morphine tolerance in the rat.British Journal of Pharmacology. 1992 Mar;105(3):591-6.PMID 1628146
  9. ↑Hoffmann O, Wiesenfeld-Hallin Z. The CCK-B receptor antagonist Cl 988 reverses tolerance to morphine in rats.Neuroreport. 1994 Dec 20;5(18):2565-8.PMID 7696605
  10. ↑Maldonado R, Valverde O, Ducos B, Blommaert AG, Fournie-Zaluski MC, Roques BP. Inhibition of morphine withdrawal by the association of RB 101, an inhibitor of enkephalin catabolism, and the CCKB antagonist PD-134,308.British Journal of Pharmacology. 1995 Mar;114(5):1031-9.PMID 7780637
  11. ↑Valverde O, Roques BP. Cholecystokinin modulates the aversive component of morphine withdrawal syndrome in rats.Neuroscience Letters. 1998 Mar 6;244(1):37-40.PMID 9578139
  12. ↑Bradwejn J, Koszycki D, Paradis M, Reece P, Hinton J, Sedman A. Effect of CI-988 on cholecystokinin tetrapeptide-induced panic symptoms in healthy volunteers.Biological Psychiatry. 1995 Dec 1;38(11):742-6.PMID 8580227
  13. ↑Adams JB, Pyke RE, Costa J, Cutler NR, Schweizer E, Wilcox CS, Wisselink PG, Greiner M, Pierce MW, Pande AC. A double-blind, placebo-controlled study of a CCK-B receptor antagonist, CI-988, in patients with generalized anxiety disorder.Journal of Clinical Psychopharmacology. 1995 Dec;15(6):428-34.PMID 8748432
  14. ↑van Megen HJ, Westenberg HG, den Boer JA, Slaap B, van Es-Radhakishun F, Pande AC. The cholecystokinin-B receptor antagonist CI-988 failed to affect CCK-4 induced symptoms in panic disorder patients.Psychopharmacology (Berlin). 1997 Feb;129(3):243-8.PMID 9084062
  15. ↑Goddard AW, Woods SW, Money R, Pande AC, Charney DS, Goodman WK, Heninger GR, Price LH. Effects of the CCK(B) antagonist CI-988 on responses to mCPP in generalized anxiety disorder.Psychiatry Research. 1999 Mar 22;85(3):225-40.PMID 10333376
  16. ↑Pande AC, Greiner M, Adams JB, Lydiard RB, Pierce MW. Placebo-controlled trial of the CCK-B antagonist, CI-988, in panic disorder.Biological Psychiatry. 1999 Sep 15;46(6):860-2.PMID 10494457
  17. ↑Le Guen S, Mas Nieto M, Canestrelli C, Chen H, Fournié-Zaluski MC, Cupo A, Maldonado R, Roques BP, Noble F. Pain management by a new series of dual inhibitors of enkephalin degrading enzymes: long lasting antinociceptive properties and potentiation by CCK2 antagonist or methadone.Pain. 2003 Jul;104(1-2):139-48. DOI 10.1016/S0304-3959(02)00486-4PMID 12855323

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