Theophylline is an antagonist of adenosine in human forearm arterioles

The pharmacodynamics of theophylline in humans is attributed to the inhibition of phosphodiesterase activity, a concept based on in vitro studies using drug concentrations much higher than those achieved by therapeutic doses. Recent in vitro studies suggest that theophylline might act as an antagonist of adenosine. This hypothesis was tested in hypertensives by assessing the effect of theophylline on adenosine mediated vasodilation. Drugs were infused into the brachial artery while forearm blood flow (venous plethysmography) was continuously monitored. Adenosine, infused cumulatively (5, 15, and 50 micrograms/min for 3 min each; n = 5), caused a dose-dependent vasodilation that was clearly blunted in the presence of theophylline in a dose not affecting basal arterial flow (1000 micrograms/min for 20 min). On the contrary, papaverine, a selective phosphodiesterase activity inhibitor, infused at two increasing doses (100 and 300 micrograms/min for 20 min, n = 5), did not affect adenosine mediated vasodilation. Our data show that theophylline acts as a specific antagonist of adenosine in humans, an effect which might be relevant for its pharmacological action.