Effects of FPL 55712, ETYA and Aminophylline upon Ascaris-Induced Bronchoconstriction in Cynomolgus Monkeys

Abstract

Dose-related impairment of pulmonary functions was induced in artificially respired, anesthetized cynomolgus monkeys by inhalation of aerosolized Ascaris antigen (AA) in ascending doses. The effects of pharmacologic agents were assessed by increases in threshold Ascaris dose (TAD). TAD were defined as the doses of AA needed for 20% increase in pulmonary resistance and 15% decrease in compliance. Inhaled FPL 55712, an SRS-A antagonist (1.24 mg through-the-valve dose; TTVD), and 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of lipoxygenase and cyclooxygenase (1.0 mg TTVD) resulted in significant increases in the geometric means of TAD for changes in compliance (p < 0.01). The effects of both agents upon resistance were of borderline significance. Orally administered aminophylline (30 mg/kg) had no significant effect upon mean TAD for resistance or compliance. The activities of FPL 55712 and ETYA suggest that spasmogenic leukotrienes are involved in the pulmonary allergic reactions in cynomolgus monkeys.