The antiinflammatory profile of (5H-dibenzo[a,d]-cyclohepten-5-ylidene)acetic acid (WY-41,770), an agent possessing weak prostaglandin synthetase inhibitory activity that is devoid of gastric side effects.
Wy-41,770 [(5H-dibenzo[a,d]cyclohepten-5-ylidene)acetic acid], a novel acrylic acid, was compared to indomethacin and aspirin in standard antiinflammatory, analgesic and antipyretic animal models. The acute antiinflammatory, analgesic and antipyretic activity of Wy-41,770 (oral ED50S 50-170 mg/kg) was similar to aspirin; however, it was considerably more potent orally in adjuvant arthritis in the rat (ED50, 16 mg/kg) and urate-induced synovitis in the dog (ED50, 4.5 mg/kg). Wy-41,770 was a weak inhibitor of prostaglandin biosynthesis and did not inhibit either 5- or 15-lipoxygenase. Furthermore, the cellular migration characteristic of carrageenan pleurisy was not affected by Wy-41,770. Unlike a majority of NSAIDs, it produced no gastric irritation in rats after either acute or chronic oral administration over the range 400-800 mg/kg. The major mechanism of action of Wy-41,770 has yet to be identified but does not seem to involve interference of arachidonic acid metabolism.
D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000517:prevention & control; D002351:Carrageenan; D016861:Cyclooxygenase Inhibitors; D003986:Dibenzocycloheptenes / Q000494:pharmacology* / Q000627:therapeutic use; D004064:Digestive System / Q000187:drug effects; D015232:Dinoprostone; D004487:Edema / Q000517:prevention & control; D005334:Fever / Q000517:prevention & control; D006941:Hyperesthesia / Q000517:prevention & control; D066298:In Vitro Techniques; D007509:Irritants; D016859:Lipoxygenase Inhibitors; D008264:Macrophages / Q000378:metabolism; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010998:Pleurisy / Q000517:prevention & control; D011453:Prostaglandins / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles / Q000378:metabolism; D013585:Synovitis / Q000517:prevention & control; D015002:Yeast, Dried
D000085:Acetates; D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D003986:Dibenzocycloheptenes; D007509:Irritants; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D011458:Prostaglandins E; C042276:Wy 41770; D002351:Carrageenan; D015232:Dinoprostone