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Are tolfenamic acid and tenidap dual inhibitors of 5-lipoxygenase and cyclo-oxygenase?

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Abstract

Tolfenamic acid and tenidap have been reported to be dual inhibitors of cyclo-oxygenase and 5-lipoxygenase. In this study inhibition of 5-lipoxygenase by tenidap and tolfenamic acid in plasma-free leukocyte suspensions (IC50 values=10 μM) required concentrations more than 100 fold higher than those which inhibited cyclo-oxygenase (IC50 values=0.05 and 0.02 μM respectively). The potencies of tolfenamic acid and tenidap as cyclo-oxygenase inhibitors were markedly reduced in blood (IC50=6.5 and 10 μM respectively) and neither significantly inhibited 5-lipoxygenase. Since both drugs also failed to inhibit 5-lipoxygenase in rat bloodex vivo, we conclude that, at physiological levels of plasma proteins, tolfenamic acid and tenidap are selective cyclo-oxygenase inhibitors.

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  1. Bioscience I Department, ICI Pharmaceuticals, Mereside, Alderley Park, SK10 4TG, Macclesfield, Cheshire, UK

    K. E. Proudman & R. M. McMillan

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  1. K. E. Proudman
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  2. R. M. McMillan
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Proudman, K.E., McMillan, R.M. Are tolfenamic acid and tenidap dual inhibitors of 5-lipoxygenase and cyclo-oxygenase?. Agents and Actions 34, 121–124 (1991). https://doi.org/10.1007/BF01993255

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  • DOI: https://doi.org/10.1007/BF01993255

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