New pharmacological data on the bronchospasmolytic activity of bamifylline

Abstract

Resistance to lung inflation and blood pressure were monitored together with biological and radioimmunological determination of circulating thromboxane A2 (TxA2) in anaesthetized guinea-pig. Bamifylline, a 2-benzyl-[4,5-d]-imidazopyrimidine derivative, and theophylline were compared for their antagonistic activity against the pulmonary effect of histamine (0.05 mumol/kg i.v.), leukotriene C4 (LTC4, 0.016 mumol/kg i.v.), platelet-activating factor (PAF, 0.0002 mumol/kg i.v.) and acetylcholine (0.1 mumol/kg i.v.). Bamifylline, as well as theophylline, showed a dose-dependent antagonistic activity against both bronchoconstriction and TxA2 generation induced by the above agonists. However, except for histamine where the two compounds were equiactive, bamifylline was 2 times more potent than theophylline. The maximal inhibitory activity was found against bronchoconstriction induced by PAF (ED50 = 6.5 mumol/kg i.v.) followed by histamine (ED50 = 9.5 mumol/kg i.v.), acetylcholine (ED50 = 24.3 mumol/kg i.v.) and LTC4 (ED50 = 31.6 mumol/kg i.v.). Bamifylline (3, 10, 30, 100 mumol/kg i.v.) and theophylline (3, 10, 30, 100 mumol/kg i.v.) protected guinea-pig from antigen-induced bronchoconstriction and TxA2 generation in ovalbumin actively sensitized animals. Also in this series of experiments bamifylline was more potent than theophylline, the ED50 being 9.3 mumol/kg i.v. and 22.9 mumol/kg i.v., respectively. These pharmacological data represent new support for the protecting effect of bamifylline against respiratory damage induced by well known anaphylaxis mediators.