Antiasthma activity of the novel antihistamine E-4716 in guinea pigs in vivo.

The effects of E-4716, a novel antihistamine compound, on histamine-induced bronchoconstriction, platelet activating factor (PAF)- or antigen-induced airway hyperreactivity, eosinophil infiltration, and airway microvascular leakage were compared with those of reference drugs in guinea pigs in vivo. E-4716 (300 microg/kg, i.v. or i.p.) suppressed histamine-induced bronchoconstriction in nonsensitized anesthetized guinea pigs and effectively inhibited acetylcholine-induced bronchial hyperreactivity in nonsensitized animals 24 h after PAF aerosol exposure. E-4716 also attenuated antigen-induced acute respiratory distress and suppressed histamine-induced airways hyperreactivity in conscious sensitized animals 24 h after antigen exposure, but did not affect the increased number of eosinophils in the bronchoalveolar lavage fluid. E-4716 300 microg/kg, i.v. or 1 mg/ml by inhalation (60 breaths) inhibited both PAF- and antigen-induced airway microvascular leakage. This in vivo profile of activity, comprising antihistamine, antihyperreactivity and antiexudative effects, suggests that E-4716 is of potential therapeutic value as an antiasthma and/or antiallergic drug.