ANTIASTHMA ACTIVITY OF THE NOVEL ANTIHISTAMINE E-4716 IN GUINEA-PIGS IN-VIVO

The effects of E-4716, a novel antihistamine compound, on histamine-in duced bronchoconstriction, platelet activating factor (PAF)-or antigen -induced airway hyperreactivity, eosinophil infiltration, and airway m icrovascular leakage were compared with those of reference drugs in gu inea pigs in vivo. E-4716 (300 mu g/kg, i.v. or i.p.) suppressed hista mine-induced bronchoconstriction in nonsensitized anesthetized guinea pigs and effectively inhibited acetylcholine-induced bronchial hyperre activity in nonsensitized animals 24 h after PAF aerosol exposure. E-4 716 also attenuated antigen-induced acute respiratory distress and sup pressed histamine-induced airways hyperreactivity in conscious sensiti zed animals 24 h after antigen exposure, but did not affect the increa sed number of eosinophils in the bronchoalveolar lavage E-4716300 mu g /kg, i.v. or 1 mg/ml by inhalation (60 breaths) inhibited both PAF- an d antigen-induced airway microvascular leakage. This in vivo profile o f activity, comprising antihistamine, antihyperreactivity an antiexuda tive effects, suggests that E-4716 is of potential therapeutic value a s an antiasthma and/or antiallergic drug.