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.