As a bronchodilator, theophylline has been utilized in the treatment of respiratory diseases-such as asthma and chronic obstructive pulmonary disease (COPD)-for well over half a century. However, its clinical application has faced certain limitations due to the narrow therapeutic window (where the effective therapeutic dose is relatively close to the toxic dose), its propensity for side effects, and its comparatively weak bronchodilating efficacy. In recent years, however, in-depth research into the pharmacological mechanisms of theophylline-coupled with advancements in pharmaceutical formulations-has elevated the standing of theophylline-based drugs in the management of respiratory diseases; this is particularly true following the discovery of the anti-inflammatory and immunomodulatory effects associated with low-dose theophylline therapy. The pharmacological actions of theophylline are remarkably diverse and can be summarized as follows:
First, it induces bronchodilation, thereby exerting an anti-asthmatic effect.
Second, it stimulates the respiratory center, enhances the contractile force of the diaphragm, and alleviates diaphragmatic fatigue.
Third, it promotes the ciliary beating of the airway epithelium, thereby enhancing mucociliary clearance.
Fourth, it exerts positive inotropic and diuretic effects, thereby improving cardiac function; furthermore, it possesses anti-inflammatory and immunomodulatory properties within the airways.
To date, over 300 distinct theophylline-based drugs and their derivatives have been identified; among those commonly employed in clinical practice are aminophylline, proxyphylline, and doxofylline. Doxofylline, in particular, demonstrates a bronchodilating potency 10 to 15 times greater than that of aminophylline; moreover, it exhibits a longer duration of action and possesses antitussive (cough-suppressing) properties. Crucially, because doxofylline lacks adenosine receptor antagonist activity, it does not induce the central nervous system or gastrointestinal adverse reactions typically associated with conventional theophylline, nor does it carry a risk of drug dependence.
