Pharamcological Characterization of a Novel Long-acting Histamine H_1 Receptor Antagonist, KAA-276

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概要

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• The pharmacological profile of a newly synthesized histamine H_1 receptor antagonist, KAA-276 (1-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-yl]-5-[2-[4-(2-carboxyethyl)-phenyl]ethyl]-1,5-diazacyclooctane sulfate), was characterized. In a H_1 receptor binding assay in vitro, KAA-276 inhibited [^3H]mepyramine binding to guinea pig cerebellar membrane preparations with an IC_<50> of 0.66 nM. The inhibitory potency of KAA-276 was greater than that of terfenadine, but similar to that of astemizole and letotifen. KAA-276 antagonized the histamine-induced constriction of ileum and trachea isolated from guinea pigs in a dose-dependent manner with a concomitant reduction in the maximum response. Furthermore, the inhibitory effect of KAA-276 on histamine induced contraction was potentiated depending on the duration of preincubation time and revealed an irreversible property. KAA-276 given orally, intraduodenally, and by inhalation significantly inhibited histamine-induced bronchoconstriction dose-dependently in guinea pigs. Inhalation of KAA-276 exhibited inhibitory activity with a rapid onset and long duration, while intraduodenal administration resulted in action with a slow onset. Therefore, KAA-276,an irreversible and selective histamine, H_1 receptor antagonist, was shown to be a useful drug for therapeutic strategies against bronchial asthma when administered by the aerosol route.

• 公益社団法人日本薬学会の論文
• 1998-04-15

著者

• Momose Den-ichi

  Central Research Laboratory Kissei Pharmaceutical Co. Ltd.

• Kobayashi Toshiro

  Central Research Laboratory Kissei Pharmaceutical Co. Ltd.

• Takehana Yasuo

  Central Research Laboratory Kissei Pharmaceutical Co. Ltd.

• SHINAGAWA Kazuhiko

  Centlar Research Laboratory, Kissei Pharmaceutical Co. Ltd.,

• TSUYUKI Shogo

  Central Research Laboratory, Kissei Pharmaceutical Co. Ltd.,

• TOKUTAKE Yoshiki

  Central Research Laboratory, Kissei Pharmaceutical Co. Ltd.,

• SATO Masaaki

  Central Research Laboratory, Kissei Pharmaceutical Co. Ltd.,

• Shinagawa Kazuhiko

  Centlar Research Laboratory Kissei Pharmaceutical Co. Ltd.

• Tsuyuki Shogo

  Central Research Laboratory Kissei Pharmaceutical Co. Ltd.

• Tokutake Yoshiki

  Central Research Laboratory Kissei Pharmaceutical Co. Ltd.

• Sato Masaaki

  Central Research Laboratory Kissei Pharmaceutical Co. Ltd.

関連論文

• Pharamcological Characterization of a Novel Long-acting Histamine H_1 Receptor Antagonist, KAA-276
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