, Volume 2, Issue 1, pp 37–46 | Cite as

An overview of nonsteroidal antiinflammatory agents (NSAIA)

  • Walter L. Norton
  • M. A. P. Meisinger


Since the rediscovery of willow bark extract (salicin) in 1763, there has been a continuing effort to improve efficacy and reduce the side effects of antiinflammatory agents through chemical modification and innovation. The second-generation NSAIA's, phenylbutazone and indomethacin, provided clear support for the idea that these objectives were obtainable. The success of steroid programs in enhancing potency and modifying side effects, coupled with the development of effective screening techniques for identifying antiinflammatory activity, stimulated an enormous effort to develop new NSAIA's. The products of this effort are now coming to the clinic.

Although less successful than the steroid program in enhancing potency, the effort has succeeded in changing and reducing side effects. As a result, the clinician has a greater choice of agents for dealing with individual patient variability and achieving greater patient acceptance.


Public Health Steroid Internal Medicine Indomethacin Antiinflammatory Activity 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Stone, E. 1763. An account of the success of the bark of the willow in the cure of agues (letter to the Right Hon. George Earl).Phil. Trans. 53:195.Google Scholar
  2. 2.
    Maclagan, T.J. 1876. The treatment of acute rheumatism by salicin.Lancet 1:342.Google Scholar
  3. 3.
    Bywaters, E.G.L. 1963. The history of salicylates.In Salicylates. A. St.J. Dixon, M.J.H. Smith, B.K. Martin, and P.H.N. Wood, editors. Little, Brown, Boston. Chap. 3.Google Scholar
  4. 4.
    Martin, B.K. 1963. Significant factors in the history of aspirin.In Salicylates. A. St.J. Dixon, M.J.H. Smith, B.K. Martin, and P.H.N. Wood, editors. Little, Brown, Boston. Chap. 6.Google Scholar
  5. 5.
    Selye, H. 1953. Use of “granuloma pouch” technic in the study of antiphlogistic corticoids.Proc. Soc. Exp. Biol. Med. 82:328.Google Scholar
  6. 6.
    Robert, A., andI.E. Nezamis. 1957. The granuloma pouch as a routine assay for antiphlogistic compounds,Acta Endocrinol. 25:105.Google Scholar
  7. 7.
    Winter, C.A., andC.C. Porter. 1957. Effect of alterations in side chain upon antiinflammatory and liver glycogen activities of hydrocortisone esters.J. Am. Pharm. Assoc., Sci. Ed. 46:515.Google Scholar
  8. 8.
    Reichenberg, H.K. von. 1962. Phenylbutazone. Edward Arnold Ltd., London.Google Scholar
  9. 9.
    Shen, T.Y., T.B. Wincholz, A. Rosegay, B.E. Witzel, A.N. Wilson, J.D. Willett, W.J. Holtz, R.L. Ellis, A.R. Matzuk, S. Lucas, C.H. Stammer, F.W. Holly, L.H. Sarett, E.A. Risley, G.W. Nuss, andC.A. Winter. 1963. Non-steroid antiinflammatory agents.J. Am. Chem. Soc. 85:488.Google Scholar
  10. 10.
    Winder, C.V. 1967. Pharmacology of fenamates.Ann. Phys. Med., Suppl. 7:49.Google Scholar
  11. 11.
    Shen, T.Y. 1965. Synthesis and biological activity of some indomethacin analogs.In International Symposium on Nonsteroidal Anti-Inflammatory Drugs, Milan, 1964. Excerpta Medica International Congress Series No. 82, New York. 13.Google Scholar
  12. 12.
    Scherrer, R.A. 1974. Introduction to the chemistry of anti-inflammatory and antiarthritic agents.In Anti-Inflammatory Agents. R.A. Scherrer and M.W. Whitehouse, editors. Academic Press, New York. 29.Google Scholar
  13. 13.
    Shen, T.Y. 1974. Nonacidic antiarthritic agents and the search for new classes of agents.In Anti-Inflammatory Agents. Vol. 1. R.A. Scherrer and M.W. Whitehouse, editors. Academic Press, New York. 179.Google Scholar
  14. 14.
    Hart, F.D., S.B. Logie, E.C. Huskisson, andR.T. Littler. 1970. Hepatic effects of fenclozic acid.Ann. Rheum. Dis. 29:684.Google Scholar
  15. 15.
    Van Arman, C.G., E.A.Risley, G.W.Nuss, H.B.Hucker, and D.E.Duggan. The pharmacology of sulindac.Scand. J. Rheumatol. In press.Google Scholar
  16. 16.
    Vane, J.R. 1971. Inhibition of prostaglandin synthesis as a mechanism of action of aspirin-like drugs.Nature, New Biol. 231:232.Google Scholar
  17. 17.
    Lombardino, J.G., I.G. Otterness, andE.H. Wiseman. 1975. Acidic anti-inflammatory agents-Correlations of some physical, pharmacologie, and clinical data.Arzneim. -Forsch. 24:1629.Google Scholar
  18. 18.
    Wax, J., C.V. Winder, D.K. Tessman, andM.D. Stephens. 1975. A sensitive method for the comparative bioassay of nonsteroidal anti-inflammatory compounds in adjuvant-induced primary inflammation in the rat.J. Pharmacol. Exp. Ther. 192:166.Google Scholar
  19. 19.
    Wax, J., C.V. Winder, D.K. Tessman, andM.D. Stephens. 1975. Comparative activities, tolerances, and safety of nonsteroidal anti-inflammatory agents in rats.J. Pharmacol. Exp. Ther. 192:172.Google Scholar
  20. 20.
    Ham, E.A., V.J. Cirillo, M. Zanetti, T.Y. Shen, andF.A. Kuehl, Jr. 1972. Studies on the mode of action on nonsteroidal anti-inflammatory agents.In Prostaglandins in Cellular Biology. P.W. Ramwell and B.B. Pharris, editors. Plenum Press, New York. 34.Google Scholar
  21. 21.
    Winter, C., andL. Flataker. 1965. Nociceptive thresholds as affected by parenteral administration of irritants and of various antinociceptive drugs.J. Pharmacol. Exp. Ther. 148:373.Google Scholar
  22. 22.
    Collier, H.O.J., L.C. Dinneen, C.A. Johnson andC. Schneider. 1968. The abdominal constriction response and its suppression by analgesic drugs in the mouse.Br. J. Pharmacol. Chemother. 32:295.Google Scholar
  23. 23.
    Swingle, K.F., T.J. Grant, andD.C. Kvam. 1971. Quantal responses in the Randall-Selitto assay.Proc. Soc. Exp. Biol. Med. 137:536.Google Scholar
  24. 24.
    Ward, J.R., M. Klauber, J.E. Gleichert, R.F. Willkens, J. Rotstein, W.A. Katz, andW.E. Pierce. 1973. A controlled multicenter trial of 2,3-dihydro-1-H-pyridino-(2,3-b)(1,4)-thiazine-2-one in rheumatoid arthritis.J. Clin. Pnarmacol. 12:218.Google Scholar
  25. 25.
    Brogden, R.N., T.M. Speight, andG.S. Avery. 1974. Ketoprofen: A preliminary report of its pharmacological activity and therapeutic efficacy in rheumatic disorders.Drugs 8:168.Google Scholar
  26. 26.
    Erdmann, G.H. 1974. Oxyphenbutazone and flufenamic acid in the treatment of osteoarthritis of the knee.S. Afr. Med. J. 48:947.Google Scholar
  27. 27.
    Meyers, O.L., O.P. Quantock, P.G. Joubert, D.P. DuP. Louw, D.F. Marais, W.A. McDonald Scott, andF.O. Muller. 1974. A multicentre trial of voltaren in the treatment of rheumatoid arthritis.S. Afr. Med. J. 48:2013.Google Scholar
  28. 28.
    Scharff, E.U. 1974. A double-blind comparison of phenylbutazone and aspirin in osteoarthritis.Curr. Ther. Res. 16:1264.Google Scholar
  29. 29.
    Calabro, J.J. 1975. Long-term reappraisal of indomethacin.Drug Ther. 5(2):46.Google Scholar
  30. 30.
    Maibach, E. 1976. European experiences with tolmetin in the treatment of rheumatic diseases.Curr. Ther. Res. 19(3):350.Google Scholar
  31. 31.
    Royer, G.L., T.E. Moxley, M.S. Hearron, A. Miyara, andB.M. Shenker. 1975. long-term double-blind trial of ibuprofen and indomethacin in rheumatoid arthritis.J. Int. Med. Res. 3(3):158.Google Scholar
  32. 32.
    Brogden, R.N., R.M. Pinder, P.R. Sawyer, T.M. Speight, andG.S. Avery. 1975. Naproxen: A review of its pharmacological properties and therapeutic efficacy and use.Drugs 9:326.Google Scholar
  33. 33.
    Aylward, M. 1975. Clinical studies on alclofenac in the treatment of rheumatic diseases: A drug in question.Curr. Med. Res. Opin. 3:274.Google Scholar
  34. 34.
    Mullin, G.T., Jr. 1975. Sodium meclofenamate for rheumatoid arthritis: An early double-blind evaluation.Curr. Ther. Res. 18(6):785.Google Scholar
  35. 35.
    Dick-Smith, J.B. 1975. Drug trial design in rheumatoid arthritis: Double-blind crossover comparison of fenoprofen, aspirin, and placebo.Scand. J. Rheumatol. 4(8):101.Google Scholar
  36. 36.
    Huskisson, E.C., andP. Franchimont, editors. (1976) Clinoril in the Treatment of Rheumatic Disorders. Raven Press, New York.Google Scholar
  37. 37.
    Huskisson, E.C., F.D. Hart, G.M. Shenfield, andR.T. Taylor. 1971. Ibuprofen: A review.Practitioner 207:639.Google Scholar
  38. 38.
    Huskisson, E.C. October 1964. Recent drugs and the rheumatic diseases.Rep. Rheum. Dis. 54:1.Google Scholar
  39. 39.
    Smyth, C.J. 1972. Diagnosis and treatment in gout.In Arthritis and Allied Conditions. J.L. Hollander and D.J. McCarthy, editors. Eighth edition. Lea & Febinger, Philadelphia. 1112.Google Scholar
  40. 40.
    Will, G., andW.R. Murdoch, 1964. Treatment of rheumatic fever: Comparison of effects of aspirin and phenylbutazone.Br. Med. J. 2:281.Google Scholar
  41. 41.
    Huskisson, E.C., D.L. Woolf, H.W. Balme, J. Scott, andS. Franklyn. 1976. Four new anti-inflammatory drugs: Response and variations.Br. Med. J. 1:1048.Google Scholar
  42. 42.
    Cuthbert, M.F. 1974. Adverse reactions to nonsteroidal antirheumatic drugs.Curr. Med. Res. Opin. 2(9):600.Google Scholar

Copyright information

© Plenum Publishing Corp 1977

Authors and Affiliations

  • Walter L. Norton
    • 1
  • M. A. P. Meisinger
    • 1
  1. 1.Division of RheumatologyMedical University of South CarolinaCharleston

Personalised recommendations