Heterogeneous effect of leucotriene CysLT 1 receptor antagonists on antigen‐induced motor and inflammatory responses in guinea‐pig airways

• Published in: Autonomic & autacoid pharmacology Vol. 27; no. 1; pp. 39 - 46
• Main Authors: Alfieri, A. B., Tramontana, M., Cialdai, C., Lecci, A., Giuliani, S., Crea, A., Manzini, S., Maggi, C. A.
• Format: Journal Article
• Language: English
• Published: 01.01.2007
• ISSN: 1474-8665; 1474-8673
• DOI: 10.1111/j.1474-8673.2006.00388.x

Summary 1  The effect of montelukast or MEN91507, selective leucotriene CysLT 1 receptor antagonists, on antigen‐induced airway inflammation and bronchoconstriction were compared in anaesthetized guinea‐pigs. 2  In sensitized animals, ovalbumin (0.3 mg kg −1 , i.v.)‐induced microvascular leakage in trachea, intrapulmonary airways, total lung (parenchyma and intrapulmonary airways) and urinary bladder was reduced by MEN91507 (0.01–1  μ mol kg −1 , i.v.), whereas montelukast (0.01–1  μ mol kg −1 , i.v.) antagonized the effect of the antigen only in the lung and urinary bladder. 3  Ovalbumin (1 mg kg −1 , i.v.)‐induced bronchoconstriction was dose dependently antagonized by MEN91507 (10–30  μ mol kg −1 , i.v.), whereas the effect of montelukast (0.1–30  μ mol kg −1 , i.v.) was marginal (15–30% inhibition). Neither MEN91507 nor montelukast (30  μ mol kg −1 , i.v.) affected the bronchoconstrictor response induced by acetylcholine (0.3  μ mol kg −1 , i.v.) in sensitized animals. 4  It is concluded that montelukast and MEN91507 display a differential activity against the effect of endogenous leucotrienes, despite the fact that both compounds show a similar antagonist profile against exogenous leucotrienes acting through CysLT 1 receptors.