Phosphodiesterase Inhibitors: Their Comparative Effectiveness in Vitro in Various Organs

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Abstract
The inhibitor constants of several inhibitors for cyclic[c]AMP- and cGMP-phosphodiesterase from various organs are compared. The inhibitors were classical theophylline, papaverine and some newly developed inhibitors: an imidazolidinone compound, RO20-1724 [4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone] and 2 phthalazinol compounds, EG 467 and EG 626. Among the inhibitors tested, papverine and EG 626 were the most potent. Both compounds were extremely inhibitory to platelet [human] and arterial [rat] phosphodiesterases. EG 626 was much more inhibitory to cAMP phosphodiesterase than to cGMP phosphodiesterase in platelet- and brain-extract [mouse] and RO20-1724 was inhibitory to cAMP- but not cGMP-phosphodiesterase in brain-extract. When the skin [mouse] 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.