Leukotriene and thromboxane antagonists.

Abstract

It has been suggested that arachidonate metabolites, leukotrienes, and thromboxane may play important roles in the pathogenesis of bronchial asthma. Biologic activities of these mediators are much more potent than those of histamine and acetylcholine on a molar basis in inducing bronchoconstriction, increase in microvascular permeability, formation of mucosal edema, and mucus secretion, which are characteristic features of bronchial asthma. Furthermore, recent studies have demonstrated the presence of these mediators in plasma, BALF, and urine in asthmatic patients after allergen challenge. Therefore, the regulation of the activities of these mediators may provide a novel therapeutic approach for the treatment of bronchial asthma. A large number of 5-lipoxygenase inhibitors, peptide leukotriene antagonists, thromboxane synthase inhibitors, and thromboxane antagonists have been actively developed by the pharmaceutical industry, and there are increasing findings to demonstrate a clinical efficacy by these compounds. Among them, a thromboxane synthase inhibitor, OKY-046, first became available as an antiasthmatic agent in Japan. This is a significant step in the management of bronchial asthma. Preclinical and clinical results have suggested that these inhibitors and antagonists may be capable of inhibiting airway obstruction with airway inflammation and bronchial hyperresponsiveness, which are important characteristics of bronchial asthma. Further results from clinical studies with newly developed leukotriene and thromboxane antagonists are eagerly awaited.