MCI-826 Is a Potent and Selective Antagonist of Peptide Leukotrienes (p-LTs) and Has Characteristics Distinctive from Those of FPL 55712

[摘要] References(18)Cited-By(5)Antagonistic effects of a newly synthesized compound, (E)-2, 2-diethyl-3''-[2-[2-(4-isopropyl)thiazolyl]ethenyl]succinanilic acid sodium salt (MCI-826) on the contraction of the isolated guinea pig trachea and human bronchus induced by various agonists including peptide leukotrienes (p-LTs), histamine, acetylcholine (ACh), prostaglandin (PG) D2 and others were investigated and compared with the effects of a p-LT antagonist, FPL 55712, in some experiments. MCI-826 potently antagonized LTD4- and LTE4-induced contractions at extremely low concentrations in the isolated guinea pig trachea with pA2 values of 8.3 and 8.9, respectively, on a molar basis. These values indicated that MCI-826 is over 100 times stronger than FPL 55712. Similarly, MCI-826 at 10-8 g/ml (2.4 × 10-8 M) markedly antagonized LTD4-induced contractions of the isolated human bronchus. Although FPL 55712 fairly inhibited the 10-9 g/ml LTC4-induced contraction of the isolated guinea pig trachea, MCI-826 had little effect on the contraction at high concentrations like 3 × 10-6 g/ml (7.1 × 10-6 M). MCI-826 modestly affected the other agonist-induced contractions and the resting tonus of the isolated guinea pig trachea at 10-6 g/ml (2.4 × 10-6 M) or higher concentrations, but FPL 55712 caused fair inhibition of some of those contractions and gradually lowered the resting tonus with time. These results indicate that MCI-826 is a highly potent and selective antagonist of LTD4 and LTE4 and can be a useful tool for biological and pharmacological experiments on p-LTs.

[学科分类] 药理学

[关键词] MCI-826;FPL 55712;Leukotriene;Trachea