Abstract
A unique combination of anti-inflammatory and antiulcerogenic activities is described for 2-(2 methyl-4-chlorophenylamino)-2-imidazoline (CDMI). CDMI administered i.p. produced a dose-related decrease in aspirin-induced ulcers which persisted even in the presence of exogenously added HCI. The carrageenin-edema reducing activities of i.p. CDMI and p.o. aspirin were additive. When oral CDMI was combined with oral aspirin or oral indomethacin, the combinations also resulted in additive anti-inflammatory activities (80 and 94% vs. 52% for CDMI, 62% for aspirin and 71% for indomethacin alone). Moreover, gastric ulcerogenicity was reduced by 92% when either aspirin or indomethacin was combined with CDMI. These results indicate that CDMI and related compounds deserve further study as adjuncts to increase the margin of safety of currently used nonsteroidal anti-inflammatory agents. CDMI was also tested against a developing acute inflammatory reaction. When administered at 2 hr post carrageenin, CDMI was as effective as when it was administered 30 min before the carrageenin. These results are discussed as a possible reflection of an action on the lipoxygenase pathways of the arachidonic acid cascade that is not shared by the classical nonsteroidal anti-inflammatory agents.
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