Studies on anti-allergic action of AH 21-132, a novel isozyme-selective phosphodiesterase inhibitor in airways.

Abstract

The effects of AH 21-132, a type III and IV phosphodiesterase (PDE) inhibitor, on allergic reactions in the airway were studied by comparing them with the effects of rolipram, a type IV PDE inhibitor, and aminophylline, a non-selective PDE inhibitor. The following results were obtained: 1) AH 21-132, rolipram and aminophylline inhibited the antigen-induced contraction of isolated guinea pig tracheal muscle in vitro. 2) AH 21-132 and aminophylline inhibited antigen-induced histamine release from human lung tissue fragments. 3) Antigen-induced accumulation of inflammatory cells including eosinophils and macrophages in mice bronchoalveolar lavage fluid was clearly inhibited by AH 21-132 and rolipram, but not by aminophylline. 4) AH 21-132, rolipram and aminophylline inhibited immediate phase bronchocostriction induced by either an intravenous or an aerosol challenge of antigen in guinea pigs. 5) AH 21-132 and rolipram inhibited the aeroantigen challenge-induced late phase increase in the airway resistance in guinea pigs, but aminophylline did not. These results suggest that AH 21-132 has an anti-allergic effect in the airway and that these actions may be beneficial for the treatment of allergic bronchial asthma.