Chemistry:CI-988
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Short description: Chemical compound
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| Formula | C35H42N4O6 |
| Molar mass | 614.743 g·mol−1 |
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CI-988 (PD-134,308) is a drug which acts as a cholecystokinin antagonist, selective for the CCKB subtype. In animal studies it showed anxiolytic effects[1][2] and potentiated the analgesic action of both morphine[3] and endogenous opioid peptides,[4][5] as well as preventing the development of tolerance to opioids[6][7] and reducing symptoms of withdrawal.[8][9] Consequently, it was hoped that it might have clinical applications for the treatment of pain and anxiety in humans, but trial results were disappointing with only minimal therapeutic effects observed even at high doses.[10][11][12][13] The reason for the failure of CI-988 and other CCKB antagonists in humans despite their apparent promise in pre-clinical animal studies is unclear, although poor pharmacokinetic properties of the currently available drugs are a possible explanation,[14] and CCKB antagonists are still being researched for possible uses as adjuvants to boost the activity of other drugs.[15]
References
- ↑ "Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity". Proceedings of the National Academy of Sciences of the United States of America 87 (17): 6728–32. September 1990. doi:10.1073/pnas.87.17.6728. PMID 1975695. Bibcode: 1990PNAS...87.6728H.
- ↑ "The behavioural properties of CI-988, a selective cholecystokininB receptor antagonist". British Journal of Pharmacology 104 (1): 239–45. September 1991. doi:10.1111/j.1476-5381.1991.tb12413.x. PMID 1686205.
- ↑ "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. September 1990. doi:10.1073/pnas.87.18.7105. PMID 1698290. Bibcode: 1990PNAS...87.7105W.
- ↑ "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. March 1994. doi:10.1111/j.1749-6632.1994.tb44091.x. PMID 8185186.
- ↑ "Cholecystokinin B antagonists strongly potentiate antinociception mediated by endogenous enkephalins". The Journal of Pharmacology and Experimental Therapeutics 270 (1): 77–88. July 1994. PMID 8035345.
- ↑ "CI988, a selective antagonist of cholecystokininB receptors, prevents morphine tolerance in the rat". British Journal of Pharmacology 105 (3): 591–6. March 1992. doi:10.1111/j.1476-5381.1992.tb09024.x. PMID 1628146.
- ↑ "The CCK-B receptor antagonist Cl 988 reverses tolerance to morphine in rats". NeuroReport 5 (18): 2565–8. December 1994. doi:10.1097/00001756-199412000-00040. PMID 7696605.
- ↑ "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. March 1995. doi:10.1111/j.1476-5381.1995.tb13309.x. PMID 7780637.
- ↑ "Cholecystokinin modulates the aversive component of morphine withdrawal syndrome in rats". Neuroscience Letters 244 (1): 37–40. March 1998. doi:10.1016/s0304-3940(98)00118-9. PMID 9578139.
- ↑ "Effect of CI-988 on cholecystokinin tetrapeptide-induced panic symptoms in healthy volunteers". Biological Psychiatry 38 (11): 742–6. December 1995. doi:10.1016/0006-3223(95)00081-X. PMID 8580227.
- ↑ "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. December 1995. doi:10.1097/00004714-199512000-00007. PMID 8748432.
- ↑ "The cholecystokinin-B receptor antagonist CI-988 failed to affect CCK-4 induced symptoms in panic disorder patients". Psychopharmacology 129 (3): 243–8. February 1997. doi:10.1007/s002130050186. PMID 9084062.
- ↑ "Effects of the CCK(B) antagonist CI-988 on responses to mCPP in generalized anxiety disorder". Psychiatry Research 85 (3): 225–40. March 1999. doi:10.1016/s0165-1781(99)00015-3. PMID 10333376.
- ↑ "Placebo-controlled trial of the CCK-B antagonist, CI-988, in panic disorder". Biological Psychiatry 46 (6): 860–2. September 1999. doi:10.1016/s0006-3223(99)00090-6. PMID 10494457.
- ↑ "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. July 2003. doi:10.1016/s0304-3959(02)00486-4. PMID 12855323.
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