Antileukotriene therapy for asthma.
The role of leukotrienes (LTs) in asthma is reviewed, and research to develop anti-LT agents for this condition is described. Greater understanding of the role played by inflammatory cells and their mediators in the pathophysiology of asthma has shifted the emphasis of research from the bronchoconstriction component of the disease to the inflammatory one. LTs are believed to play a key role in the complex interplay of inflammatory cells that occurs in asthma. Inhibiting the production of LTs or blocking their receptor sites may decrease the inflammatory response and thereby provide a useful therapeutic modality. Three approaches have been used in attempts to affect the activity of LTs: inhibition of 5-lipoxygenase, inhibition of 5-lipoxygenase-activating protein, and LTD4-receptor antagonism. Investigational agents that have undergone clinical trials include zileuton (a 5-lipoxygenase inhibitor), MK-591 (a 5-lipoxygenase-activating protein inhibitor), and zafirlukast, pranlukast, and verlukast (three LT-receptor antagonists). Many studies suggest that these orally administered agents are effective, particularly with respect to the early asthmatic response to allergens and other challenges, and have a low adverse-effect profile; the reaction of greatest concern is elevation of liver enzymes, especially with zileuton. Larger trials conducted over longer periods, as well as comparative trials, will be necessary to delineate the ultimate role of these agents in asthma therapy. Because of the complexity of the inflammatory process in asthma, anti-LT agents are likely to become part of multidrug regimens. Using drugs to interfere with leukotrienes may prove beneficial in the treatment of asthma.
Larsen
J S
JS
College of Pharmacy, University of Minnesota, Minneapolis, USA.
Jackson
S K
SK
D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007249:Inflammation / Q000517:prevention & control; D015289:Leukotrienes / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*
D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; C063449:zileuton; D006918:Hydroxyurea