NEW PHARMACOLOGICAL DATA ON THE BRONCHOSPASMOLYTIC ACTIVITY OF BAMIFYLLINE

  • 1 January 1988
    • journal article
    • research article
    • Vol. 38-1  (1) , 40-44
Abstract
Resistance to lung inflation and blood pressure was 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 .mu.mol/kg i.v.), leukotriene C4 (LTC4, 0.016 .mu.mol/kg i.v.), platelet-activating factor (PAF, 0.0002 .mu.mol/kg i.v.) and acetylcholine (0.1 .mu.mol/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 .mu.mol/kg i.v.) followed by histamine (ED50 = 9.5 .mu.mol/kg i.v.), acetylcholine (ED50 = 24.3 .mu.mol/kg i.v.) and LTC4 (ED50 = 31.6 .mu.mol/kg i.v.). Bamifylline (3, 10, 30, 100 .mu.mol/kg i.v.) and theophylline (3, 10, 30, 100 .mu.mol/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 .mu.mol/kg i.v. and 22.9 .mu.mol/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.