Pharmacological studies on EB-382, a new non-steroidal antiinflammatory agent: mode of action of the antiinflammatory effects.

Abstract

The mode of action of (+/-)-2-[p-[(2-methylallyl)amino]phenyl]propionic acid (EB-382) was studied in terms of its antiinflammatory effect. EB-382 displayed a more potent inhibitory effect than that of ibuprofen on carrageenin-induced paw edema in rats, and its inhibitory action was unaffected by adrenalectomy. EB-382 had a less potent inhibitory effect than that of ibuprofen on the prostaglandin E2 biosynthesis of 3T6 mouse fibroblast cells. EB-382 displayed a much more potent inhibitory effect than that of ibuprofen on carrageenin-induced pleurisy in rats. EB-382 exhibited a dose-dependent and significant inhibitory effect on the bradykinin and prostaglandin contents released into the pleural cavity in rat pleurisy induced by carrageenin, and its potency was much higher than that of ibuprofen. EB-382 strongly inhibited the leukocyte emigration into the pleural cavity, and its potency was almost equal to that of indomethacin. EB-382 did not affect the kinin-forming enzyme and kininase activities of rat plasma in vitro. The above results suggest that the antiinflammatory effect of EB-382 was probably due to inhibition of the production of bradykinin and prostaglandins derived from emigrating leukocytes in the local inflamed tissue besides a weak inhibitory effect on prostaglandin biosynthesis.