[The effects of cyclooxygenase and lipoxygenase inhibitors: the prerequisites for more effective anti-inflammatory...

Production of effective anti-inflammatory drugs, affecting not only the acute but also the destructive phase of the inflammatory process is actual problem of pharmacology. One of the directions of production is the synthesis of drugs, which affect lipoxygenase way of metabolism of arachidonic acid, It is established that cyclooxygenase inhibitors indomethacin greater than diclophenac greater than pyroxicam greater than flurbirpophen greater than metamizol are characterized by various mechanism and degree of effect on prostaglandin profile. Indomethacin and diclophanac at high concentrations enhance the formation of lipoxygenase product 12-HETE, which causes a series of side effects and affects slightly destructive inflammatory changes. The combination with lipoxygenase inhibitor nordihydroguayretic acid (NDGA) induces inhibition of 12-HETE as well similar to the mixed cyclo-lipoxygenase blocker BW 755C. Effects analogous to BW 755C manifests glyciritinic acid at concentration of 2.10(-5)-1.10(-4) M. A correlation is found between the degree of the effect on prostaglandin synthesis and release of lysosomal enzymes from leucocytes. The possibility is discussed to produce combined preparations, affecting destructive inflammatory changes and reducing a series of side actions connected with damage of trophism of organism, by combining optimal proportions of cyclo- and lipoxygenase blockers.