Inhibitory Effect of KW-4679, an Anti-allergic Drug, on Tachykinin-Mediated Airway Response Induced by Electric Vagal Stimulation in Guinea Pigs.

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  • Ikemura Toshihide
    Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo, Co., Ltd.
  • Sasaki Yasuo
    Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo, Co., Ltd.
  • Ishii Hidee
    Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo, Co., Ltd.
  • Ohmori Kenji
    Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo, Co., Ltd.

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  • Inhibitory effect of KW-4679, an anti-allergic drug, on tachykinin-mediated airway response induced by electrical vagal stimulation in guinea pigs

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Abstract

We examined the effect of KW-4679 ((Z)-11-[(3-dimethylamino)propylidene]-6, 11-dihydrodibenz[b, e]oxepin-2-acetic acid monohydrochloride), an anti-allergic drug, on the tachykinin-mediated airway response in guinea pigs. Electrical stimulation of the vagus nerve in atropine-treated and propranololtreated guinea pigs caused a 38.1% decrease in dynamic compliance (Cdyn), which was suppressed by the combination of the tachykinin NK1-receptor antagonist (±)-CP-96345 and NK2-receptor antagonist SR 48968. KW-4679 at a dose of 3 mg/kg significantly reduced the decrease in Cdyn (P<0.05). On the other hand, KW-4679 did not inhibit substance P or neurokinin A-induced decrease in Cdyn. These results suggest that KW-4679 may inhibit the tachykininergic airway response by prejunctional inhibition of peripheral sensory nerves.

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