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The inhibitor constants of several inhibitors for cyclic AMP- and cyclic GMP-phosphodiesterase from various organs are compared. The inhibitors were classical theophyline, papaverine, and some of newly developed inhibitors: an imidazolidinone compound, RO20-1724, and two phthalazinol compounds, EG 467 and EG 626. Among the inhibitors tested, papaverine and EG 626 were found to be the most potent. Both compounds were extremely inhibitory to platelet and arterial phosphodiesterases. EG 626 was much more inhibitory to cyclic AMP phosphodiesterase than to cyclic GMP phosphodiesterase in platelet- and brain-extract and RO20-1724 was inhibitory to cyclic AMP- but not cyclic GMP-phosphodiesterase in brain-extract. When the skin adenyl cyclase was activated by AMP, the addition of theophylline blocked this activation, but EG 626 or EG 467 further potentiated the activation. These in vitro studies may serve as basic screening tests for the effectiveness of the specific phosphodiesterase inhibitors.

Phosphodiesterase Inhibitors: Their Comparative Effectiveness in Vitro in Various Organs