Pharmacological properties of the novel non-steroidal antiinflammatory agent N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2 -one.

The antiinflammatory activity of the novel pyrrolidin-2-one derivative N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-o ne (E-5110) was investigated and compared with those of indomethacin and piroxicam in various antiinflammatory, analgesic and antipyretic animal models. The acute antiinflammatory activity of E-5110 on the carrageenin paw edema was similar to that of indomethacin, and half that of piroxicam. The chronic inflammatory responses in established adjuvant- and type II collagen-induced arthritis, which are widely used models of rheumatoid arthritis, were suppressed as effectively by E-5110 as by indomethacin and piroxicam. E-5110 decreased the pleural exudate volume and inhibited leucocyte infiltration in a reversed passive Arthus reaction more potently than indomethacin, suggesting that mediators other than prostaglandin E2 may play an important role in this inflammatory process. The analgesic potency of E-5110 against inflammatory pain was similar to that of indomethacin or piroxicam, but the antipyretic activity of E-5110 was more potent than that of the reference drugs. The ulcerogenic effect of E-5110 on rat gastric mucosa was less than those of indomethacin and piroxicam. In conclusion, E-5110 is a very potent antiinflammatory compound acting against various types of inflammation, and has a favorable therapeutic index.