ONO-3144, a new anti-inflammatory drug and its possible mechanism of action.
Anti-inflammatory activities of ONO-3144 have been studied in various experimental models. This compound showed an inhibitory effect on increased vascular permeability and acute inflammation. In the carrageenin test the activity of ONO-3144 was comparable to that of indomethacin (IM), while in the dextran, albumin, yeast and scald edema test it was more potent than that of IM. Unlike IM, phenylbutazone (PB) and tiaramide (TI), ONO-3144 showed marked inhibitory effects on H2O2-induced hemolysis and lipid peroxidation. In the prostaglandin (PG) biosynthesis series, ONO-3144 did not inhibit cyclooxygenase activity but stimulated PG hydroperoxidase activity, facilitated conversion to PGH2 and also inhibited thromboxane (Tx) synthetase. The findings suggest that ONO-3144 is potentially a new type of anti-inflammatory drug. Possible sites of action of ONO-3144 are discussed.
D000818:Animals; D000893:Anti-Inflammatory Agents; D001329:Autolysis / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects*; D004487:Edema / Q000188:drug therapy; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051379:Mice; D010653:Phenylbutazone / Q000494:pharmacology; D011427:Propiophenones / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013930:Thromboxane-A Synthase / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D008054:Lipid Peroxides; D011427:Propiophenones; C037467:2-aminomethyl-4-tert-butyl-6-propionylphenol; D006861:Hydrogen Peroxide; D011451:Prostaglandin-Endoperoxide Synthases; D013930:Thromboxane-A Synthase; D010653:Phenylbutazone; D007213:Indomethacin