EFFECTS OF E-4716, A NEW ANTIHISTAMINIC WITH ANTIALLERGIC PROPERTIES,ON CHEMICAL MEDIATORS INDUCTION OF IMMUNOLOGICAL REACTIONS

The effects of E-4716 on chemical mediators were compared with those o f classical antihistaminics and other second generation (nonsedating) drugs normally used in the therapy of allergic reactions, such as aste mizole, 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 an ticholinergic activity observed. A high antihistaminic activity was al so shown in in vivo tests on chemical mediators release by compound 48 /80, histamine-induced bronchospasm in anesthetized guinea pigs and hi stamine-induced cutaneous reaction in beagle dogs. The antiallergic ac tivity was studied in passive cutaneous anaphylaxis test using ovalbum in antibodies. Astemizole and E-4716 had similar activities with ED(50 ) values of 0.8 and 0.5 mg/kg, respectively, whereas terfenadine (ED(5 0) = 4.5) was less active. E-4716 also inhibited the vascular permeabi lity response in histamine-stimulated conjunctivitis model after topic al ocular administration (ED(50) = 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 selectiv e antihistaminic and antiallergic activity by all routes of administra tion (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.