title: 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.
authors.affiliation: Research Laboratories, Institute of Biological Chemotherapy, ABC S.p.A., Turin, Italy.
authors.forename: J S
authors.initials: JS
authors.lastname: Franzone
authors.forename: R
authors.initials: R
authors.lastname: Cirillo
authors.forename: D
authors.initials: D
authors.lastname: Barone
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D004231:Diuresis / Q000187:drug effects*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects*; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014132:Trachea / Q000502:physiology
chemical_list: D000628:Aminophylline; D013806:Theophylline; D000241:Adenosine; C029797:doxofylline