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. 1992;1(2):141–143. doi: 10.1155/S0962935192000231

The in vitro free radical scavenging activity of tenidap, a new dual cyclo-oxygenase and 5-1ipoxygenase inhibitor

C S Lau 1,, J J F Belch 1
PMCID: PMC2365331  PMID: 18475454

Abstract

Tenidap, a new anti-inflammatory drug, is presently undergoing clinical studies as a treatment for rheumatoid arthritis (RA). Early pilot work has shown it to be of some benefit. Tenidap is a dual inhibitor of cyclo-oxygenase and 5-lipoxygenase enzymes. It has also been shown to modify white blood cell behaviour such as interleukin-1 production, monocyte differentiation and neutrophil degranulation. As free radicals (FRs) have been implicated in the pathogenesis of RA, we used an in vitro assay system developed by Misra and Fridovich to assess if tenidap has FR scavenging effects. Our study shows, for the first time, that tenidap has general FR scavenging effects although no effect on the superoxide anion (O2·-) could be demonstrated. This effect occurred in a dose-dependent manner at concentrations above 20 μg/ml (p < 0.005, Mann-Whitney U-test). As the therapeutic range of tenidap in serum is between 15 and 30 μg/ml such FR scavenging activity may be clinically relevant in the treatment of RA. Ex vivo confirmation of this possibility is underway.

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Selected References

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  1. Belch J. J. Eicosanoids and rheumatology: inflammatory and vascular aspects. Prostaglandins Leukot Essent Fatty Acids. 1989 Jun;36(4):219–234. doi: 10.1016/0952-3278(89)90135-x. [DOI] [PubMed] [Google Scholar]
  2. Blackburn W. D., Jr, Loose L. D., Heck L. W., Chatham W. W. Tenidap, in contrast to several available nonsteroidal antiinflammatory drugs, potently inhibits the release of activated neutrophil collagenase. Arthritis Rheum. 1991 Feb;34(2):211–216. doi: 10.1002/art.1780340213. [DOI] [PubMed] [Google Scholar]
  3. Chopra M., Belch J. J., Smith W. E. A comparison of the free radical scavenging activity of leukotrienes and prostaglandins. Free Radic Res Commun. 1988;5(2):95–99. doi: 10.3109/10715768809066916. [DOI] [PubMed] [Google Scholar]
  4. Chopra M., Scott N., McMurray J., McLay J., Bridges A., Smith W. E., Belch J. J. Captopril: a free radical scavenger. Br J Clin Pharmacol. 1989 Mar;27(3):396–399. doi: 10.1111/j.1365-2125.1989.tb05384.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dormandy T. L. An approach to free radicals. Lancet. 1983 Oct 29;2(8357):1010–1014. doi: 10.1016/s0140-6736(83)90989-3. [DOI] [PubMed] [Google Scholar]
  6. Higgs G. A., Moncada S., Vane J. R. Eicosanoids in inflammation. Ann Clin Res. 1984;16(5-6):287–299. [PubMed] [Google Scholar]
  7. Merry P., Winyard P. G., Morris C. J., Grootveld M., Blake D. R. Oxygen free radicals, inflammation, and synovitis: and synovitis: the current status. Ann Rheum Dis. 1989 Oct;48(10):864–870. doi: 10.1136/ard.48.10.864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Moilanen E., Alanko J., Asmawi M. Z., Vapaatalo H. CP-66,248, a new anti-inflammatory agent, is a potent inhibitor of leukotriene B4 and prostanoid synthesis in human polymorphonuclear leucocytes in vitro. Eicosanoids. 1988;1(1):35–39. [PubMed] [Google Scholar]
  9. Rowley D., Gutteridge J. M., Blake D., Farr M., Halliwell B. Lipid peroxidation in rheumatoid arthritis: thiobarbituric acid-reactive material and catalytic iron salts in synovial fluid from rheumatoid patients. Clin Sci (Lond) 1984 Jun;66(6):691–695. doi: 10.1042/cs0660691. [DOI] [PubMed] [Google Scholar]
  10. Scott N. A., Jennings P. E., Brown J., Belch J. J. Gliclazide: a general free radical scavenger. Eur J Pharmacol. 1991 Oct 14;208(2):175–177. doi: 10.1016/0922-4106(91)90069-t. [DOI] [PubMed] [Google Scholar]
  11. Smith D. M., Johnson J. A., Loeser R., Turner R. A. Evaluation of Tenidap (CP-66,248) on human neutrophil arachidonic acid metabolism, chemotactic potential and clinical efficacy in the treatment of rheumatoid arthritis. Agents Actions. 1990 Aug;31(1-2):102–109. doi: 10.1007/BF02003228. [DOI] [PubMed] [Google Scholar]

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