Selective inhibition of the cyclooxygenase pathway of the arachidonic acid cascade by the nonsteroidal antiinflammatory drug isoxicam

The effects of the nonsteroidal antiinflammatory drug isoxicam on prostaglandin formation by HSDM₁C₁ mouse fibrosarcoma cells grown in culture and 5-HETE(5(S)-5-hydroxy-6-trans, 8,11,14-cis eicosatetraenoic acid) formation by human leukocytes were determined. Isoxicam inhibited the formation of the cyclooxygenase product prostaglandin E₂ with an IC₅₀ of 2.0 μM. In comparison, the reference standards piroxicam and indomethacin had IC₅₀ values of 0.55 μM and 0.14 μM, respectively. Nordihydroguaiaretic acid (NDGA) was inactive up to 10 μM. Isoxicam, piroxicam, and indomethacin were relatively devoid of any significant inhibitory property on 5-lipoxygenase activity exhibiting IC₅₀ values > 500 μM. In comparison, the compounds BW755C and NDGA, known lipoxygenase inhibitors, had IC₅₀ values of 11 μM and 0.6 μM, respectively. The present findings indicated that isoxicam exhibited a selective inhibition of the cyclooxygenase pathway of the arachidonic acid cascade and that this effect may at least in part be responsible for its antiinflammatory activity observed in animals and humans.