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  • Title: Preclinical and clinical activity of zileuton and A-78773.
    Author: Bell RL, Lanni C, Malo PE, Brooks DW, Stewart AO, Hansen R, Rubin P, Carter GW.
    Journal: Ann N Y Acad Sci; 1993 Nov 30; 696():205-15. PubMed ID: 8109828.
    Abstract:
    The importance of leukotrienes as mediators of inflammation and bronchoconstriction was examined with two recently described 5-lipoxygenase inhibitors, zileuton and A-78773. Preclinical evaluation of these two molecules indicates that they are potent, selective, direct, reversible inhibitors of 5-lipoxygenase with activity in a variety of purified cells and in more complex biological systems such as whole blood, lung fragments, and tracheal tissues. In various animals models of inflammation and allergy, the molecules inhibited edema, inflammatory cell influx, and bronchospasm. These observations are consistent with the recent clinical success of zileuton in treating asthma and inflammatory bowel disease. In all preclinical systems tested thus far, A-78773 is more potent and longer acting than zileuton, indicating that the molecule could be even more effective in the clinic than zileuton and that both molecules are useful tools in defining the role of leukotrienes in preclinical and clinical settings.
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