MCI-826 is a potent and selective antagonist of peptide leukotrienes (p-LTs) and has characteristics distinctive from those of FPL 55712.
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 x 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 x 10(-6) g/ml (7.1 x 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 x 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.
Watanabe-Kohno
S
S
Department of Pharmacology, Kyoto Pharmaceutical University, Japan.
Yamamura
H
H
Nabe
T
T
Horiba
M
M
Ohata
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D002867:Chromones / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015230:Prostaglandin D2 / Q000494:pharmacology; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects*; D013189:SRS-A / Q000037:antagonists & inhibitors; D013844:Thiazoles / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D002867:Chromones; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D013189:SRS-A; D013844:Thiazoles; C077265:MCI 826; C006312:FPL 55712; D000109:Acetylcholine; D015230:Prostaglandin D2