Abstrakt: |
The antiinflammatory activity of the immuno-modulatory agent Wy-18,251 (3-( p-chlorophenyl)thiazolo-[3,2-a]benzimidazole-2-acetic acid) was examined using a variety of antiinflammatory, analgesic and antipyretic animal models in comparison to aspirin, levamisole and indomethacin. The acute antiinflammatory and analgesic activity of Wy-18,251 (ED=100-200 mg/kg, p.o.) was similar to aspirin, but in contrast to aspirin Wy-18,251 failed to demonstrate antipyretic activity. Wy-18,251 (10-100 mg/kg, p.o.) also inhibited chronic inflammatory responses in the adjuvant- and collagen-induced arthritis models. Wy-18,251 was a modest inhibitor of prostaglandin biosynthesis but did not inhibit either 5- or 15-lipoxygenase enzymes. Wy-18,251 (up to 480 mg/kg, p.o.) produced little gastrointestinal pathology in 16 h fasted rats. The combined immunomodulatory and antiinflammatory activity of Wy-18,251 suggests that this agent may have therapeutic promise in certain immunoinflammatory diseases including rheumatoid arthritis. [ABSTRACT FROM AUTHOR] |