Interference of the new antiinflammatory compound flunoxaprofen with eicosanoid formation in various biological systems.
S-(+)-2-(4-Fluorophenyl)-alpha-methyl-5-benzoxazolacetic acid (flunoxaprofen, Priaxim is a new antiinflammatory compound, which in various biological systems interferes with the generation and release of arachidonic acid metabolites of the cyclo-oxygenase pathways without affecting the formation of 5- and 12-lipoxygenase products. Flunoxaprofen reduces the concentration of thromboxane (TX)B2 (ED50 = 35.4 mg/kg p.o.) and prostaglandin (PG)E2-like activity (ED50 = 39.9 mg/kg p.o.) in the inflammatory exudate of rats 8 h after implantation of sponges soaked with carrageenan, whereas the concentration of leukotriene (LT)B4 remains in the range of that of the untreated animals (3.1 ng/ml). Flunoxaprofen inhibits cell infiltration in the exudate and this suggests that LTB4 does not initiate cell recruitment but may represent a mechanism for amplifying the inflammatory response. Using human platelets challenged with collagen, flunoxaprofen only at higher concentration (10(-4) mol/l) reduces TXB2 formation without altering generation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid. This suggests a low capacity of flunoxaprofen of affecting platelet aggregation regulated by arachidonic acid metabolites. Flunoxaprofen prevents pulmonary changes due to secondary release of TXA2 in the guinea-pig. In fact this drug prevents changes due to immunological reaction and antagonizes bronchoconstriction due to exogenous administration of histamine and LTC4.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001583:Benzoxazoles / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects; D004537:Eicosanoic Acids / Q000378:metabolism*; D005122:Exudates and Transudates / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012129:Respiratory Function Tests; D013045:Species Specificity
D000893:Anti-Inflammatory Agents; D001583:Benzoxazoles; D004537:Eicosanoic Acids; C045356:flunoxaprofen