CysLT1 Antagonism of Pranlukast, Montelukast and Zafirlukast in the Presence of Serum Albumin.
| Accession number;02A0404953 |
| Title;CysLT1 Antagonism of Pranlukast, Montelukast and Zafirlukast in the Presence of Serum Albumin. |
| Author;NAKAGAWA NAOKI(Onoyakuhinkogyo Minasesoken) FUJITA MANABU(Onoyakuhinkogyo Minasesoken) YONETOMI YASUO(Onoyakuhinkogyo Minasesoken) TANAKA MAKOTO(Onoyakuhinkogyo Minasesoken) OBATA TAKAAKI(Onoyakuhinkogyo Minasesoken) KONO SHIGEKATSU(Kyotoyakudai Yakurigaku) |
Journal Title;Japanese Pharmacology & Therapeutics
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Journal Code:Z0947A
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ISSN:0386-3603
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VOL.30;NO.3;PAGE.191-195(2002)
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| Figure&Table&Reference;FIG.1, TBL.2, REF.12 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Objectives: The aim of this study is to compare the cysLT1 antagonism in the presence of serum albumin between commercially available cysLT1 receptor antagonists, pranlukast, montelukast and zafirlukast. Methods: We examined the antagonistic activity of pranlukast, montelukast and zafirlukast on [3H] LTD4 binding to guinea pig lung membranes in the absence and presence of serum albumin. In addition, we examined the effect of pranlukast, montelukast and zafirlukast on LTD4-induced bronchoconstriction in guinea pigs by intravenous administration. Results: Pranlukast, montelukast and zafirlukast antagonized the specific binding of [3H] LTD4 to guinea pig lung membranes in the absence of human serum albumin with Ki values of 2.1.+-.0.5, 8.3.+-.2.0 and 2.6.+-.0.3nM, respectively. In the presence of 0.05% (w/v) human serum albumin, the antagonistic activity of pranlukast on cysLT1 receptors was influenced more greatly than those of montelukast and zafirlukast. On the other hand, in the presence of 1% (w/v) human serum albumin under more nearly physiological conditions, the antagonistic activity of pranlukast, montelukast and zafirlukast were almost the same with Ki Values of 68.2.+-.6.9, 95.6.+-.12.7 and 61.3.+-.2.9nM, respectively. In addition, pranlukast, montelukast and zafirlukast antagonized LTD4-induced bronchoconstriction mediated through cysLT1 receptors in a dose-dependent manner, and their respective ED50 values were 1.77, 2.18 and 2.71.MU.g/kg. Conclusions: From the above findings, it is suggested that the cysLT1 antagonism of pranlukast, montelukast and zafrrlukast are almost the same under physiological conditions. (author abst.) |
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