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Preclinical Pharmacodynamics of Anti-Inflammatory Drugs

  • Asoke Mukherjee
  • Conrad Chen
  • Lucy Jean
  • Claude B. Coutinho

Abstract

During the past three decades research into the development of anti-inflammatory (AI) drugs has given rise in the main to the cyclooxygenase inhibitors. More recent efforts, based on a better understanding of the pathophysiology of the inflammatory process, have led to the development of unique and novel molecular entities as potential candidates for use in the treatment of inflammation. However, lack of suitable animal models that mimic the human disease and specific markers to follow immunological response that might possibly be associated with the disease process have made the selection of which new drug to take into clinical trials more difficult. This review discusses some of the advantages and disadvantages of animal models used routinely for the evaluation of AI agents and includes some suggestions as to how one might approach the development of newer models that may help identify novel AI drugs with varying mechanisms of therapeutic action.

Keywords

Ellagic Acid Systemic Autoimmune Disease Cyclooxygenase Inhibitor Purine Nucleoside Phosphorylase Transgenic Animal Model 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Arthritis Foundation (1985). History of Rheumatology in the United States., pp. 115–142.Google Scholar
  2. Barden, J. A., and J. L. Deeker (1971). Mycoplasma hyorhinis swine arthritis. 1. clinical and microbiological features. Arth. Rheum.14, 193–201Google Scholar
  3. Billingham, M. E. J. (1990). Models of arthritis and the search for antiarthritic drugs. In M. L. E.Orme (Ed.), Anti-rheumatic Drugs Pergamon Press, New York. pp.1–47.Google Scholar
  4. Biotard, C. (1990). Pathophysiology of the autoimmune diseases. Klin. Wochenschr 68, 1–9.Google Scholar
  5. Brune, K., P. Graf, and M. Glatt (1976). Inhibition of prostaglandin synthesis in vivo by nonsteroidal anti-inflammatory drugs: evidence for the importance of pharmacokinet ics. Agents and Actions 6, 159–164.PubMedCrossRefGoogle Scholar
  6. Campbell, I. L., and L. C. Harrison (1990). Molecular pathology of type I diabetes. Mol. Biol. 2, 299–309.Google Scholar
  7. Cannon, W. B., and J.E. Uridil (1921). Studies on the condition of activity in endocrine glands. VIII. Some effects on the denervated heart of stimulating the nerves of the liver. Am. J. Physiol. 58, 353–354.Google Scholar
  8. Caufield, J. P., A. Hein, R. Dynesius-Trentham, and D. Trentham (1982). Morphologic demonstration of two stages in the development of type II collagen-induced arthritis. Lab. Invest. 46, 321–343.Google Scholar
  9. Chritadoss, P., C. S. David, M. Shenoy, and S. Keve (1990). Alpha transgene in B10 mice suppresses the development of myasthenia gravis. Immunogenetics 31, 241–244.Google Scholar
  10. Cole, B. C. and G. H. Cassell (1979). Mycoplasma infections as models of chronic joint inflammation. Arth. Rheum. 22, 1375–1381.CrossRefGoogle Scholar
  11. Dinarello, C. A. (1984). Interleukin-1., Rev. Infec. Dis. 6, 51–95.CrossRefGoogle Scholar
  12. Dustin, M. L., R. Rothlein, A. K. Bhan, C. A. Dinarello, and T. A. Springer (1986). Induction by IL-1 and interferon-gamma: Tissue distribution, biochemistry, and function of natural adherence molecule (ICAM-1). J. Immunol. 137, 245–254.Google Scholar
  13. Folkman, J., and M. Klagsbrum (1987). Angiogenic factors. Science, 235 442–447.PubMedCrossRefGoogle Scholar
  14. Friedman, S. M., D. N. Posnett, J. R. Tumang, B. C. Cole, and M. K. Crow (1991). A potential role for microbial superantigens in the pathogenesis of systemic autoimmune disease. Arth. Rheum. 34, 468–480.CrossRefGoogle Scholar
  15. Gilbertsen, R. B., and J. C. Sircar (1990). Enzyme cascades: Purine metabolism and immunosuppression. In C. Hansch (Ed.), Comprehensive Medicinal Chemistry Vol. 2, Pergamon Press, New York. pp. 443–480.Google Scholar
  16. Halliwell, B., J. R. Hoult, and D. R. Blake (1988) Oxidants, inflammation, and anti-inflammatory drugs. FASEB J., 2, 2867–2873.Google Scholar
  17. Hamberg, M., J. Svensson, and B. Samuelsson (1975). Thromboxanes: A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc. Natl. Acad. Sci. 72, 2994–2998.Google Scholar
  18. Hench, P. S., E. C. Kendall, C. H. Slocumb, and H. F. Polley (1949). Effect of a hormone of the adrenal cortex (17 hydroxy-11 dehydrocorticosterone), compound E and of pituitary adrenocortico-tropic hormone on rheumatoid arthritis: Preliminary report. Proc. Staff Meet. Mayo Clin. 24, 181.Google Scholar
  19. Lieberman, R., M. Katzper, M.Cooper, C. Myers, G. Burke, L. Sanathanan, and C. Peck (1991). Bayesian PK concentration controlled trials of suram in anticancer therapy. Clin. Pharmacol. Ther. 49, 155.Google Scholar
  20. Loewi, O., and E. Navratil (1926). Uber humorale Ubertragbarkeit der Herznervenwirkung. X. Mitteilung Uber das Schicksal des Vagusstoff. Pflugers Arch. Gesamte Physiol., 214 678–688.CrossRefGoogle Scholar
  21. Marry, P., M. Grootveld, and D.R. Blake (1990). Free radicals and hypoxic reperfusion injury. A mechanism producing persistent synovitis. Topical Reviews Arthritis Rheumatism Council, London.Google Scholar
  22. Martin, D. A., and E. W. Gelfand (1981). Biochemistry of diseases of immunodevelopment. Ann. Rev. Biochem. 50, 845–877.Google Scholar
  23. Mizel, S. B. (1989). The interleukins. FASEB.J. 3, 2379–2388.Google Scholar
  24. Needleman, P., M. Minkes, and A. Raz (1976). Thromboxanes: Selective biosynthesis and distinct biological properties. Science, 193 163–165.Google Scholar
  25. Nickerson, C. L., K. L. Hogen, H. S. Luthra, and C. S. David (1990). Effect of H-2 genes on expression of HLA-B27 and Yersinia-induced arthritis. Scan. J. Rheum. Suppl. 87, 85–90.CrossRefGoogle Scholar
  26. Otterness, I. G., and D. J. Gans (1988). Nonsteroidal anti-inflammatory drugs: an analysis of the relationship between laboratory animal and clinical doses, including species scaling. J. Pharm. Sci. 77, 790–794.Google Scholar
  27. Phillips, P. E. (1986). Infectious agents in the pathogenesis of rheumatoid arthritis. Seminars in Arth. Rheum. 16, 1–10.Google Scholar
  28. Popovic, S., and R. R. Barlett (1986). Disease modifying activity of HWA 486 on the development of SLE in MRL/1-mice. Agents and Actions 12, 313–314.CrossRefGoogle Scholar
  29. Rainsford, K. D. (1982). Adjuvant polyarthritis in rats: Is this a satisfactory model for screening antiarthritic drugs? Agents and Actions 12, 452–458.Google Scholar
  30. Rordorf-Adam, C., B. Rordorf, D. Serban, and A. Pataki (1986): The effects of anti-inflammatory agents on the serology and arthritis of the MRL 1pr/lpr mouse. Agents and Actions 19, 309–310.Google Scholar
  31. Samuelsson, B. (1983). Leukotrienes: Hypersensitivity reactions and inflammation. Science 220, 568–575.Google Scholar
  32. Shinagawa, H. (1990). The effects of HLA class II genes on the susceptability to autoimmune thyroid diseases. Fukuoka Igaku Zasshi. Fukuoka Acta Medica 97–111.Google Scholar
  33. Sircar, J. C., and R. B. Gilbertsen (1988). Purine nucleoside phosphorylase (PNP) inhibitors: Potentially selective immunosuppressive agents. Drugs of the Future 13, 653–668.Google Scholar
  34. Springer, T. A., M. A. Dustin, T. K. Kishimoto, and S. D. Marlin (1987). The lymphocyte function-associated LFA-1, CD 2, and LFA-3 molecules: Cell adhesion receptors of the immune system. Ann. Rev. Immunol. 5, 223–252.Google Scholar
  35. Stuart, J. M., A. S. Townes and A. H. Kang (1982). The role of collagen autoimmunity in animal models and human disease. J. Invest. Derm. 79, 121S- 127S.Google Scholar
  36. Taurog, J. D., J. P. Durand, F. A. el-Zaatari, and R. E. Hammer (1988). Studies of HLA-B27 associated disease. Am. J. Med. 85, 59–60.Google Scholar
  37. Trentham, D. E., A. S. Townes, and A. H. Kang (1977). Autoimmunity to type II collagen: an experimental model of arthritis. J. Expt. Med., 146 857–868.CrossRefGoogle Scholar
  38. van Arman, C. G., R. P. Carlson, E. A. Risley, R. H. Thomas, and G. W. Nuss (1970). Inhibitory effects of indomethacin, aspirin and certain other drugs on inflammation induced in rat and dog by carrageenin, sodium urate and ellagic acid. J. Pharmacol. Exp. Ther., 175 459–468.PubMedGoogle Scholar
  39. Vane, J. R. (1971). Inhibition of prostaglandin synthesis as a mechanism of action for aspirin like drugs. Nature (New Biol.), 231 232–235.Google Scholar
  40. Winter, C. A., E. A. Risley, and C. W. Nuss (1962). Carrageenin induced edema in hind paw of the rat as an assay for anti-inflammatory drugs. Proc. Soc. Expt. Biol. Med., 111 544–547.Google Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Asoke Mukherjee
    • 1
  • Conrad Chen
    • 1
  • Lucy Jean
    • 1
  • Claude B. Coutinho
    • 1
  1. 1.Center for Drug Evaluation and ResearchFood and Drug AdministrationRockvilleUSA

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