Leukotrienes and the mechanism by which the LTRAs block their asthma-related effects

The past several decades of research have culminated in the recognition of asthma as a chronic inflammatory disease of the airways and the knowledge that cysteinyl leukotrienes (CysLTs) are important mediators in the inflammatory process. These potent bronchoconstrictors inhibit mucociliary transport while stimulating mucus secretion, thereby contributing to airway obstruction. They also increase microvascular permeability, which results in airway edema; recruit inflammatory cells; and increase expression of proinflammatory cytokines. CysLTs produce these asthma-related effects by interacting with the CysLT1 receptor. Thus, the leukotriene receptor antagonists (LTRAs) were specifically developed as antiasthma agents that provide controller effects by blocking this receptor. The 2 LTRAs available for clinical use in the United States--montelukast and zafirlukast--are potent inhibitors of leukotriene D4 binding to the CysLT1 receptor.