[环加氧酶和脂加氧酶抑制剂的作用:更有效的抗炎组合的先决条件]。

M Vlaskovska
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引用次数: 0

摘要

生产有效的抗炎药物,既影响炎症过程的急性期,又影响炎症过程的破坏期,是药理学的实际问题。生产方向之一是影响脂氧合酶花生四烯酸代谢方式的药物的合成,建立了环氧合酶抑制剂吲哚美辛大于双氯非那酸大于pyroxicam大于氟脲酚大于metamizol对前列腺素谱的影响具有不同的机制和程度。高浓度吲哚美辛和双氯芬酸可促进脂氧合酶产物12-HETE的形成,产生一系列副作用,影响轻度破坏性炎症变化。与脂氧合酶抑制剂去二氢瓜泥酸(NDGA)联合可诱导对12-HETE的抑制,效果与混合环-脂氧合酶阻滞剂BW 755C相似。与BW 755C类似的作用表现为2.10(-5)-1.10(-4)m浓度下的甘氨酸酸,对前列腺素合成的影响程度与白细胞溶酶体酶的释放之间存在相关性。讨论了通过组合环氧合酶和脂氧合酶阻滞剂的最佳比例来生产联合制剂,影响破坏性炎症变化并减少与生物体营养损害相关的一系列副作用的可能性。
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[The effects of cyclooxygenase and lipoxygenase inhibitors: the prerequisites for more effective anti-inflammatory combinations].

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.

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