A novel anti-asthmatic quinone derivative, AA-2414 with a potent antagonistic activity against a variety of spasmogenic prostanoids

The anti-asthmatic activity of AA-2414 [(±)-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl-7-phenylheptanoic acid)] has been studied in vivo and in vitro . Experimental allergic asthma was inhibited by orally administered AA-2414 in a dose-dependent manner. AA-2414, 0.08∼1.25 mg/kg (p.o.), inhibited the bronchoconstriction in guinea pigs induced by a prostaglandin endoperoxide analogue (U-46619), leukotriene D 4 (LTD 4 ), and platelet activitating factor (PAF) with a long duration of action. The compound did not inhibit histamine-induced bronchoconstriction. AA-2414 reduced the induction of pulmonary inflation caused by LTD 4 aerosol inhalation. AA-2414 competitively inhibited the contractile response to U-46619 in guinea pig tracheal and parenchymal strips and dog saphenous vein strips with pA2 values of 7.69, 8.29 and 6.79, respectively. Furthermore, the contractile responses of guinea pig tracheal strip to PGD 2 , 9 a , 11s-PGF 2 and PGF 2 a were inhibited with pA2 values of 7.20, 7.79 and 5.71, respectively. These results suggest that AA-2414, a quinone derivative, is a novel, potent and orally active antagonist of a variety of spasmogenic prostanoids.