Effects of the new antiallergic drug epinastine and ketotifen on repeated antigen challenge-induced airway hyperresponsiveness in rats.

Airway hyperresponsiveness (AHR) is a critical component in bronchial asthma, probably associated with airway inflammation. The effects of epinastine (WAL-801 CL, CAS 80012-43-7), a new antiallergic drug, and ketotifen on AHR were investigated with a new AHR model in rats. Male Wistar rats which were actively sensitized with DNP-Ascaris (DNP-Asc) antigen, were challenged by inhaling DNP-Asc 3 times every 48 h. The airway responsiveness to inhaled ACh was determined 24 h after the last antigen challenge by modified Konzett-Rössler method under anesthesia with urethane. Antiallergic drugs were given orally 1 h before each antigen challenge in case of single treatment, and 3 times a day for 5 days in case of chronic treatment. The airway responsiveness to inhaled ACh was significantly increased after the repeated antigen challenge. Single treatments with epinastine and ketotifen did not inhibit AHR induced by repeated antigen challenge. On the other hand, chronic epinastine and ketotifen treatments, significantly inhibited the enhancement of AHR. From the above results, it is suggested that chronic treatments with epinastine and ketotifen are effective even for therapy of AHR.