Toshihide Ikemura, Yasuo Sasaki, Hidee Ishii and Kenji Ohmori
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo, Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411, Japan
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 propranolol-treated 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.
KW-4679, Tachykinin, Vagal stimulation
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