Are tolfenamic acid and tenidap dual inhibitors of 5-lipoxygenase and cyclo-oxygenase?
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 microM) required concentrations more than 100 fold higher than those which inhibited cyclo-oxygenase (IC50 values = 0.05 and 0.02 microM respectively). The potencies of tolfenamic acid and tenidap as cyclo-oxygenase inhibitors were markedly reduced in blood (IC50 = 6.5 and 10 microM respectively) and neither significantly inhibited 5-lipoxygenase. Since both drugs also failed to inhibit 5-lipoxygenase in rat blood ex vivo, we conclude that, at physiological levels of plasma proteins, tolfenamic acid and tenidap are selective cyclo-oxygenase inhibitors.
Proudman
K E
KE
Bioscience I Department, ICI Pharmaceuticals, Macclesfield, Cheshire, UK.
McMillan
R M
RM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D001798:Blood Proteins / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D000078183:Oxindoles; D051381:Rats; D013929:Thromboxane B2 / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D016859:Lipoxygenase Inhibitors; D000078183:Oxindoles; D062367:ortho-Aminobenzoates; D016718:Arachidonic Acid; C009500:tolfenamic acid; D013929:Thromboxane B2; C062866:tenidap