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Doxofylline, an adenosine-nonblocking xanthine, does not induce cardiostimulant effects
R Cirillo1, E Grossi, J S Franzone
1ABC Pharmaco-Toxicological Research Laboratories, Turin, Italy.
Research Communications in Chemical Pathology and Pharmacology
|July 1, 1989
Summary
Doxofylline, an anti-asthmatic drug, shows potent bronchodilator effects without the cardiac side effects of theophylline. It is a safer alternative for treating lung diseases, especially with beta 2-adrenergic agonists.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Respiratory Medicine
Background:
- Theophylline, a xanthine derivative, is a bronchodilator but causes significant extrapulmonary side effects.
- Adenosine plays a role in cardiovascular and respiratory functions.
- Doxofylline is a novel anti-asthmatic drug designed to avoid theophylline's side effects.
Purpose of the Study:
- To compare the cardiac activity of doxofylline and theophylline.
- To investigate the interaction of doxofylline and theophylline with adenosine.
- To evaluate the potential of doxofylline in treating chronic obstructive lung disease.
Main Methods:
- In vitro studies using guinea pig right and left atrial preparations.
- In vivo studies on anesthetized cats.
- Assessment of atrial rate, contractile force, and blood pressure.
Main Results:
- Doxofylline exhibited minimal cardiac effects compared to theophylline.
- Theophylline caused dose-dependent positive chronotropic and hypotensive effects.
- Doxofylline was significantly less potent than theophylline in antagonizing adenosine-induced cardiodepression.
Conclusions:
- Doxofylline possesses a favorable cardiac safety profile compared to theophylline.
- Doxofylline's non-adenosine-blocking mechanism contributes to its reduced cardiac side effects.
- Doxofylline is a promising therapeutic option for chronic obstructive lung disease, potentially in combination therapies.