Potential anti-inflammatory effects of 5-lipoxygenase inhibition--exemplified by the leukotriene synthesis inhibitor BAY X 1005.
Leukotrienes have been identified in various pathophysiologies. The leukotrienes LTB4 and LTC4 are assigned to inflammation. 5-lipoxygenase inhibitors which inhibit the synthesis of LTA4 being the precursor of both LTB4 and LTC4 appear to have only a limited antiinflammatory potential. 5-lipoxygenase inhibitors are represented by direct and indirect inhibitors, the latter competing with substrate transfer from the five-lipoxygenase activating protein (FLAP) to the 5-lipoxygenase enzyme. 5-lipoxygenase inhibition under experimental condition results in inhibition of edema formation, neutrophil infiltration, smooth muscle contraction after antigen challenge and prevention of early and late allergic reactions. Only in the cysteinyl-leukotriene-driven pathophysiology of allergic asthma and allergic rhinitis 5-lipoxygenase inhibition appears to provide symptomatic relief. Yet, the overall-antiinflammatory effect in man in far less than expected, but may be outweighed by the nearly total lack of any side effects of 5-lipoxygenase inhibition per se.
Müller-Peddinghaus
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BAYER AG, Business Group Pharma Institute for Cardiovascular and Arteriosclerosis Research Wuppertal, Germany.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016859:Lipoxygenase Inhibitors; D011804:Quinolines; C079315:2-(4-(quinolin-2-yl-methoxy)phenyl)-2-cyclopentylacetic acid