INHIBITORY EFFECT OF KW-4679, AN ANTIALLERGIC DRUG, ON TACHYKININ-MEDIATED AIRWAY RESPONSE INDUCED BY ELECTRIC VAGAL-STIMULATION IN GUINEA-PIGS

We examined the effect of KW-4679 opylidene]-6,11-dihydro-dibenz[b,e]o xepin-2-acetic acid monohydrochloride), an anti-allergic drug, on the tachykinin-mediated airway response in guinea pigs. Electrical stimula tion of the vagus nerve in atropine-treated and propranolol-treated gu inea pigs caused a 38.1% decrease in dynamic compliance (C-dyn), which was suppressed by the combination of the tachykinin NK1-receptor anta gonist (+/-)-CP-96345 and NK2-receptor antagonist SR 48968. KW-4679 at a dose of 3 mg/kg significantly reduced the decrease in C-dyn (P < 0. 05) On the other hand, KW-4679 did not inhibit substance P or neurokin in A-induced decrease in C-dyn. These results suggest that KW-4679 may inhibit the tachykininergic airway response by prejunctional inhibiti on of peripheral sensory nerves.