Effects of E-4716, a new antihistaminic with antiallergic properties, on chemical mediators induction of immunologic reactions.

The effects of E-4716 on chemical mediators were compared with those of classical antihistaminics and other second generation (nonsedating) drugs normally used in the therapy of allergic reactions, such as astemizole, terfenadine and ebastine, in a series of in vitro and in vivo tests. In vitro, antihistaminic activity was demonstrated in a test on isolated organs and a binding test on histamine receptors, with no anticholinergic activity observed. A high antihistaminic activity was also shown in in vivo tests on chemical mediators release by compound 48/80, histamine-induced bronchospasm in anesthetized guinea pigs and histamine-induced cutaneous reaction in beagle dogs. The antiallergic activity was studied in passive cutaneous anaphylaxis test using ovalbumin antibodies. Astemizole and E-4716 had similar activities with ED50 values of 0.8 and 0.5 mg/kg, respectively, whereas terfenadine (ED50 = 4.5) was less active. E-4716 also inhibited the vascular permeability response in histamine-stimulated conjunctivitis model after topical ocular administration (ED50 = 0.002, 0.0002, 0.015 and 1.2% at 30 min and 6, 12 and 24 h, respectively). E-4716 had a high and selective antihistaminic and antiallergic activity by all routes of administration (oral, i.v., i.p., topical ocular and inhalation). These results, combined with its low toxicity and lack of central effects, indicate that E-4716 has excellent potential for therapeutic use.