The antiinflammatory activity of the immunomodulator Wy-18,251 (3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid).
The antiinflammatory activity of the immunomodulatory 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 (ED50 = 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.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use* / Q000633:toxicity; D000700:Analgesics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use* / Q000633:toxicity; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000209:etiology; D001241:Aspirin / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use* / Q000633:toxicity; D003094:Collagen; D005334:Fever / Q000188:drug therapy / Q000209:etiology; D005753:Gastric Mucosa / Q000187:drug effects; D006941:Hyperesthesia / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007978:Levamisole / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains
D000276:Adjuvants, Immunologic; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D001562:Benzimidazoles; D016718:Arachidonic Acid; D007978:Levamisole; C029171:tilomisole; D003094:Collagen; D001241:Aspirin