CI-988

CI-988
CI-988
CI-988 structure.png
식별자
  • 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
CAS 번호
  • 130332-27-3
펍켐 CID
켐스파이더
유니
켐벨
화학 및 물리적 데이터
공식C35H42N4O6
어금질량614.743 g·mits−1
3D 모델(JSmol)
  • C[C@@](Cc1c[nH]c2c1cccc2)(C(=O)NC[C@@H](c3ccc3)NC(=O)CC(=O)ONC(=O)OC4C5CC6CC(C5)CC4C6
  • InChI=1S/C35H42N4O6/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/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)/t21?,22?,24?,25?,29-,32?,35+/m0/s1
  • 키:FVQSSYMRZKLFDR-ZABPBAJSA-N
(iii)

CI-988(PD-134,308)은 CCKB 하위 유형에 선택적으로 셀시스토킨 길항제 역할을 하는 약물이다.동물 연구에서 그것은 항불안제 효과를[1][2] 보여주었고,[4][5] 오피오이드에[6][7] 대한 내성의 발달을 방지하고 금단 증상을 감소시킬 뿐만 아니라 모르핀과[3] 내생성 오피오이드 펩타이드 모두의 진통 작용을 촉진시켰다.[8][9]따라서 인간의 고통과 불안을 치료하기 위한 임상적 응용이 있을 수 있기를 기대했지만, 고용량에서도 최소한의 치료효과만 관찰되어 실험 결과는 실망스러웠다.[10][11][12][13]비록 현재 이용 가능한 약을 가난한pharmacokinetic 속성이 가능한 explanation,[14]과 CCKB 경쟁 상대 모두 여전히 adjuvants 가능한 변경에서는 acti를 진작할 수가 연구되고 있CI-988과 인간의 다른 CCKB 경쟁 상대 모두 사전 임상 동물 연구에서 그들이 명백한 약속에도 불구하고 그 실패의 이유는 밝혀지지 않고 있다.vity다른 [15]약물의null

참조

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  2. ^ Singh L, Field MJ, Hughes J, Menzies R, Oles RJ, Vass CA, Woodruff GN (September 1991). "The behavioural properties of CI-988, a selective cholecystokininB receptor antagonist". British Journal of Pharmacology. 104 (1): 239–45. doi:10.1111/j.1476-5381.1991.tb12413.x. PMC 1908271. PMID 1686205.
  3. ^ Wiesenfeld-Hallin Z, Xu XJ, Hughes J, Horwell DC, Hökfelt T (September 1990). "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 of the United States of America. 87 (18): 7105–9. Bibcode:1990PNAS...87.7105W. doi:10.1073/pnas.87.18.7105. PMC 54692. PMID 1698290.
  4. ^ Durieux C, Derrien M, Maldonado R, Valverde O, Blommaert A, Fournié-Zaluski MC, Roques BP (March 1994). "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. 713: 355–7. doi:10.1111/j.1749-6632.1994.tb44091.x. PMID 8185186. S2CID 23317834.
  5. ^ Valverde O, Maldonado R, Fournie-Zaluski MC, Roques BP (July 1994). "Cholecystokinin B antagonists strongly potentiate antinociception mediated by endogenous enkephalins". The Journal of Pharmacology and Experimental Therapeutics. 270 (1): 77–88. PMID 8035345.
  6. ^ Xu XJ, Wiesenfeld-Hallin Z, Hughes J, Horwell DC, Hökfelt T (March 1992). "CI988, a selective antagonist of cholecystokininB receptors, prevents morphine tolerance in the rat". British Journal of Pharmacology. 105 (3): 591–6. doi:10.1111/j.1476-5381.1992.tb09024.x. PMC 1908430. PMID 1628146.
  7. ^ Hoffmann O, Wiesenfeld-Hallin Z (December 1994). "The CCK-B receptor antagonist Cl 988 reverses tolerance to morphine in rats". NeuroReport. 5 (18): 2565–8. doi:10.1097/00001756-199412000-00040. PMID 7696605.
  8. ^ Maldonado R, Valverde O, Ducos B, Blommaert AG, Fournie-Zaluski MC, Roques BP (March 1995). "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. 114 (5): 1031–9. doi:10.1111/j.1476-5381.1995.tb13309.x. PMC 1510310. PMID 7780637.
  9. ^ Valverde O, Roques BP (March 1998). "Cholecystokinin modulates the aversive component of morphine withdrawal syndrome in rats". Neuroscience Letters. 244 (1): 37–40. doi:10.1016/s0304-3940(98)00118-9. PMID 9578139. S2CID 34384142.
  10. ^ Bradwejn J, Koszycki D, Paradis M, Reece P, Hinton J, Sedman A (December 1995). "Effect of CI-988 on cholecystokinin tetrapeptide-induced panic symptoms in healthy volunteers". Biological Psychiatry. 38 (11): 742–6. doi:10.1016/0006-3223(95)00081-X. PMID 8580227. S2CID 1096074.
  11. ^ Adams JB, Pyke RE, Costa J, Cutler NR, Schweizer E, Wilcox CS, et al. (December 1995). "A double-blind, placebo-controlled study of a CCK-B receptor antagonist, CI-988, in patients with generalized anxiety disorder". Journal of Clinical Psychopharmacology. 15 (6): 428–34. doi:10.1097/00004714-199512000-00007. PMID 8748432.
  12. ^ van Megen HJ, Westenberg HG, den Boer JA, Slaap B, van Es-Radhakishun F, Pande AC (February 1997). "The cholecystokinin-B receptor antagonist CI-988 failed to affect CCK-4 induced symptoms in panic disorder patients". Psychopharmacology. 129 (3): 243–8. doi:10.1007/s002130050186. PMID 9084062. S2CID 12570838.
  13. ^ Goddard AW, Woods SW, Money R, Pande AC, Charney DS, Goodman WK, et al. (March 1999). "Effects of the CCK(B) antagonist CI-988 on responses to mCPP in generalized anxiety disorder". Psychiatry Research. 85 (3): 225–40. doi:10.1016/s0165-1781(99)00015-3. PMID 10333376. S2CID 140209273.
  14. ^ Pande AC, Greiner M, Adams JB, Lydiard RB, Pierce MW (September 1999). "Placebo-controlled trial of the CCK-B antagonist, CI-988, in panic disorder". Biological Psychiatry. 46 (6): 860–2. doi:10.1016/s0006-3223(99)00090-6. PMID 10494457. S2CID 5801419.
  15. ^ Le Guen S, Mas Nieto M, Canestrelli C, Chen H, Fournié-Zaluski MC, Cupo A, et al. (July 2003). "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. 104 (1–2): 139–48. doi:10.1016/s0304-3959(02)00486-4. PMID 12855323. S2CID 38514264.