Jpn. J. Pharmacol. 71 (2), 179-182 (1996)

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

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.

Keywords: KW-4679, Tachykinin, Vagal stimulation

Copyright© The Japanese Pharmacological Society 1996

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