KC-404: A potential anti-allergic agent with antagonistic action against slow reacting substance of anaphylaxis.
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- NISHINO Keigo
- Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd.
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- OHKUBO Hideo
- Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd.
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- OHASHI Mitsuo
- Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd.
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- HARA Saburo
- Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd.
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- KITO Junshi
- Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd.
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- IRIKURA Tsutomu
- Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd.
書誌事項
- タイトル別名
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- 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
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- Jpn.J.Pharmacol.
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Jpn.J.Pharmacol. 33 (2), 267-278, 1983
公益社団法人 日本薬理学会
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詳細情報
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- CRID
- 1390001204284888320
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- NII論文ID
- 130000835348
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- NII書誌ID
- AA00691188
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- COI
- 1:CAS:528:DyaL3sXitV2ks7c%3D
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- ISSN
- 13473506
- 00215198
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- NDL書誌ID
- 2627944
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- PubMed
- 6193303
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可