Inhibition of prostaglandin synthetase and carrageenan-induced edema by tricyclic analogs of flufenamic acid.
A group of tricyclic analogs of flufenamic acid were tested for their ability to inhibit both the biosynthesis of prostaglandin and carrageenan-induced inflammation of the rat paw. All had activity greater than phenylbutazone as inhibitors of prostaglandin synthetase, with SK&F 22908 being as active as flufenamic acid. The anti-inflammatory activities of these compounds correlated only to a minor degree with the inhibition of prostaglandin biosynthesis. The data support the position that within this series of compounds inhibition of prostaglandin synthetase and non-steroidal antiinflammatory activity, as well as ulcerogenic liability, may be an expression of different mechanisms.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002417:Cattle; D016861:Cyclooxygenase Inhibitors; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005439:Flufenamic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D051381:Rats; D012669:Seminal Vesicles / Q000648:ultrastructure; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D005439:Flufenamic Acid; D002351:Carrageenan; D006899:Mixed Function Oxygenases