The effect of diphenylamine derivatives such as diclofenac sodium, mefenamic acid and lobenzarit disodium on arachidonic acid metabolism in rat peritoneal macrophages was examined. Lobenzarit disodium has no effect on prostaglandin E2 production as measured by radioimmunoassay although two other diphenylamine derivatives have a potent inhibito activity. Three diphenylamine derivatives have no effect on Ca2+ ionophore-stimulated release of radioactivity from (3H)arachidonic acid-labeled macrophages. HPLC analysis revealed that lobenzarit disodium had no effect on the synthesis of lipoxygenase products as observed in diclofenac sodium and mefenamic acid. It is concluded that lobenzarit disodium, although its fundamental chemical structure resembles diclofenac sodium and mefenamic acid, has no inhibitory activity on arachidonic acid metabolism, suggesting that immunomodulatory activities of lobenzarit disodium are manifested without interfering with arachidonic acid metabolism.
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