Effects of enprofylline and theophylline may show the role of adenosine

Abstract

It is well established that at low and clinically relevant concentrations theophylline (and caffeine) exerts antagonism at cell surface receptor sites for adenosine. However, it is not known which actions of theophylline are due to adenosine antagonism, because theophylline apparently activates other cellular mechanisms at the same low concentrations. Investigations into the actions of xanthines and their structure activity relationships have identified xanthine compounds like enprofylline (3-propylxanthine) that only has some actions in common with theophylline and that has a negligible ability to antagonize adenosine. Enprofylline is a more potent smooth muscle relaxant and antiasthmatic drug than theophylline but does not produce, e.g., theophylline-like diuretic effects, CNS-stimulant behavioural effects (restlessness - seizures), gastric secretory effects and release of free fatty acids. It is proposed that pharmacodynamic dissimilarities between enprofylline and theophylline may indicate physiological roles of adenosine.