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• W2052210446 endingPage "278" @default.
• W2052210446 startingPage "267" @default.
• W2052210446 abstract "The mode of action of a novel compound, 3-isobutyryl-2-isopropylpyrazolo [1,5-a]pyridine (KC-404), as a potential anti-allergic agent has been investigated. KC-404 was shown to have a direct bronchodilator activity in guinea pig trachea in vitro and in anesthetized guinea pig in vivo. In addition, KC-404 had a fairly selective antagonistic action against slow reacting substance of anaphylaxis (SRS-A) on guinea pig ileum in vitro. In anesthetized guinea pigs, ED50 values for intravenously and intraduodenally injected KC-404 to inhibit SRS-A-induced bronchoconstriction were 0.0014 and 0.0065 mg/kg, respectively. Much higher doses were required to inhibit bronchospasms produced by histamine or particularly by acetylcholine. Orally administered KC-404, 0.001 to 0.1 mg/kg, also showed a selective inhibitory effect on increased vascular permeability by intradermal SRS-A in guinea pigs and rats. KC-404 inhibited the immunological release of mediators, notably SRS-A from sensitized guinea pig chopped lung in vitro at 10−8 to 10−4 g/ml. In vivo, the release of SRS-A, but not of histamine, mediated by a nonreaginic antibody in the peritoneal cavity of sensitized rats was inhibited by KC-404 at oral doses above 3 mg/kg. In a similar anaphylactic reaction but mediated by a reaginic antibody, KC-404 also inhibited SRS-A release at intraperitoneal doses of 2.5 to 10 mg/kg. The inhibitory activity on histamine release was less than half of that on SRS-A release. These results indicate that KC-404 is an orally active compound with a unique mode of action to inhibit preferentially both the effects and immunological release of SRS-A." @default.
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• W2052210446 date "1983-01-01" @default.
• W2052210446 modified "2023-10-14" @default.
• W2052210446 title "KC-404: A potential anti-allergic agent with antagonistic action against slow reacting substance of anaphylaxis." @default.
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• W2052210446 doi "https://doi.org/10.1254/jjp.33.267" @default.
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