Doxofylline and theophylline are xanthines with partly different mechanisms of action in animals

Abstract

Doxofylline is a new antibronchospastic drug, recently introduced in therapy, with pharmacological properties like theophylline, a potent adenosine receptor antagonist. The authors have investigated the occurrence, after doxofylline administration, of the typical side-effects displayed by methylxanthines in general. The EC50 values of doxofylline in inhibiting the adenosine-induced relaxation of tracheal smooth muscle and the negative inotropic effect induced by adenosine on isolated guinea-pig atria were about 15 and 10 times greater respectively than those of aminophylline. Again, doxofylline increased diuresis only slightly (+15.8) with 20 mg/kg os, and did not increase sodium excretion; aminophylline, on the contrary, produced a dose-dependent increase in urine volume and natriuresis. In mice, aminophylline (6-24 mg/kg given intraperitoneally) dose-dependently increased locomotor activity, while doxofylline (6-24 mg/kg, i.p.) had no effect on behaviour. In anaesthetized guinea-pigs, doxofylline, in continuous intravenous infusion (0.5 ml/min) at 10 and 30 mg/ml, demonstrated fewer toxic effects than those induced by aminophylline: the effect on diastolic blood pressure, on threshold-dose for convulsions, on death-time and on lethal dose came later than with aminophylline. Finally, doxofylline did not affect gastric acid secretion, either in vitro or in vivo, unlike theophylline. The lack of side-effects with doxofylline indicates that this drug can be used safely and effectively in the treatment of obstructive lung disease.