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: J S Franzone, R Cirillo, D Barone
• Journal: Drugs under experimental and clinical research (Drugs Exp Clin Res) Vol. 14 Issue 7 Pg. 479-89 ( 1988) ISSN: 0378-6501 [Print] Switzerland
• PMID: 3240706 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Aminophylline
• Theophylline
• Adenosine
• doxofylline

Topics

• Adenosine (pharmacology)
• Aminophylline (pharmacology)
• Animals
• Diuresis (drug effects)
• Gastric Acid (metabolism)
• Gastric Mucosa (drug effects)
• Guinea Pigs
• In Vitro Techniques
• Male
• Mice
• Motor Activity (drug effects)
• Muscle Contraction (drug effects)
• Muscle, Smooth (physiology)
• Myocardial Contraction (drug effects)
• Natriuresis (drug effects)
• Rats
• Rats, Inbred Strains
• Reference Values
• Theophylline (analogs & derivatives, pharmacology)
• Trachea (physiology)