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Heterogeneous effect of leucotriene CysLT1 receptor antagonists on antigen-induced motor and inflammatory responses in guinea-pig airways

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Summary

1 The effect of montelukast or MEN91507, selective leucotriene CysLT1 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 mol kg−1, i.v.), whereas montelukast (0.01–1 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 mol kg−1, i.v.), whereas the effect of montelukast (0.1–30 mol kg−1, i.v.) was marginal (15–30% inhibition). Neither MEN91507 nor montelukast (30 mol kg−1, i.v.) affected the bronchoconstrictor response induced by acetylcholine (0.3 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 CysLT1 receptors.
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Keywords: MEN 91507; allergy; asthma; bronchoconstriction; montelukast; urinary bladder

Document Type: Research Article

Affiliations: 1: Department of Pharmacology, School of Pharmacy, Central University of Venezuela, Caracas, Venezuela 2: Pharmacology Department, Menarini Ricerche, via Sette Santi 1, 50131 Florence, Italy 3: Pharmacokinetics and Metabolism Department, Menarini Ricerche, via Tito Speri 10, 00040 Pomezia, Rome Italy

Publication date: 01 January 2007

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