KC-404: A potential anti-allergic agent with antagonistic action against slow reacting substance of anaphylaxis.

  • NISHINO Keigo
    Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd.
  • OHKUBO Hideo
    Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd.
  • OHASHI Mitsuo
    Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd.
  • HARA Saburo
    Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd.
  • KITO Junshi
    Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd.
  • IRIKURA Tsutomu
    Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd.

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タイトル別名
  • KC-404 A Potential Anti Allergic Agent

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抄録

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.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 33 (2), 267-278, 1983

    公益社団法人 日本薬理学会

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