Antileukotriene therapy for asthma. 1996

J S Larsen, and S K Jackson
College of Pharmacy, University of Minnesota, Minneapolis, USA.

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.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006918 Hydroxyurea An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. Hydroxycarbamid,Hydrea,Oncocarbide
D001249 Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). Asthma, Bronchial,Bronchial Asthma,Asthmas
D015289 Leukotrienes A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. Leukotriene
D016859 Lipoxygenase Inhibitors Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES. 5-Lipoxygenase Inhibitor,Lipoxygenase Inhibitor,12-Lipoxygenase Inhibitors,15-Lipoxygenase Inhibitors,5-Lipoxygenase Inhibitors,Arachidonate 12-Lipoxygenase Inhibitors,Arachidonate 15-Lipoxygenase Inhibitors,Arachidonate 5-Lipoxygenase Inhibitors,Inhibitors, Lipoxygenase,12 Lipoxygenase Inhibitors,12-Lipoxygenase Inhibitors, Arachidonate,15 Lipoxygenase Inhibitors,15-Lipoxygenase Inhibitors, Arachidonate,5 Lipoxygenase Inhibitor,5 Lipoxygenase Inhibitors,5-Lipoxygenase Inhibitors, Arachidonate,Arachidonate 12 Lipoxygenase Inhibitors,Arachidonate 15 Lipoxygenase Inhibitors,Arachidonate 5 Lipoxygenase Inhibitors,Inhibitor, 5-Lipoxygenase,Inhibitor, Lipoxygenase,Inhibitors, 12-Lipoxygenase,Inhibitors, 15-Lipoxygenase,Inhibitors, 5-Lipoxygenase,Inhibitors, Arachidonate 12-Lipoxygenase,Inhibitors, Arachidonate 15-Lipoxygenase,Inhibitors, Arachidonate 5-Lipoxygenase

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