Preclinical pharmacological studies have demonstrated that cysLT1 receptor antagonists, such as zafirlukast, montelukast, and pobilukast, are potent and selective antagonists of cysteinyl leukotriene (cysLT) activity. In vitro, these agents compete with [3H]LTD4 for binding to cysLT1 receptors present on guinea pig and human lung cell membranes. Both zafirlukast and montelukast have affinities that are approximately two times greater than that of the natural ligand, LTD4. These agents block LTD4- and LTE4-induced contractions of isolated guinea pig trachea, but do not antagonize LTC4-induced contractions, which are putatively mediated by a different LT receptor, cysLT2. The cysLT2 receptor, however, has not yet been found in human airway smooth muscle. In animal models, these drugs inhibit LTD4-, LTE4-, and antigen-induced bronchoconstriction, reduce inflammatory markers in models of pulmonary inflammation, and inhibit antigen-induced late-phase bronchoconstriction. This preclinical profile suggests that cysLT1 receptor antagonists may be useful in treating inflammatory conditions of the respiratory system, such as asthma and allergic rhinitis. Aharony D. Pharmacology of leukotriene receptor antagonists.