Inhibitory effect of KW-4679, an anti-allergic drug, on tachykinin-mediated airway response induced by electrical vagal stimulation in guinea pigs.
We examined the effect of KW-4679 ((Z)-11-[(3-dimethylamino) propylidene]-6,11-dihydro-dibenz[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.
Ikemura
T
T
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo, Co., Ltd., Shizuoka, Japan.
Sasaki
Y
Y
Ishii
H
H
Ohmori
K
K
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects*; D003990:Dibenzoxepins / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D008297:Male; D000069605:Olopatadine Hydrochloride; D010880:Piperidines / Q000494:pharmacology; D018039:Receptors, Tachykinin / Q000187:drug effects*; D014630:Vagus Nerve / Q000502:physiology*
D018926:Anti-Allergic Agents; D001549:Benzamides; D001713:Biphenyl Compounds; D003990:Dibenzoxepins; D010880:Piperidines; D018039:Receptors, Tachykinin; D000069605:Olopatadine Hydrochloride; C073839:SR 48968; C066892:CP 96345