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

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Abstract
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.