Theophylline-like properties of xanthine analogs.

Theophylline and other methylxanthines display a large number of biological effects, some of which are clinically important. The effects of these compounds are commonly ascribed to an inhibition of cyclic AMP breakdown. However, it becomes actually evident that another mechanism, namely adenosine receptor antagonism, could be responsible for certain methylxanthine effects. It could be of interest to find new compounds displaying only one of these mechanisms, either phosphodiesterase inhibition or adenosine receptor antagonism. We have studied several synthetic imidazol[1,2a]pyrazines, some of which display theophylline-like pharmacological properties at lower doses than theophylline. We showed that some of these compounds inhibited mitogen-induced [3H]-thymidine uptake by human lymphocytes, which is consistent with increases in cyclic AMP levels: the most efficient compounds were those which were better phosphodiesterase inhibitors than theophylline and poorer adenosine receptor antagonists.