Adachi K, Numano F
Jpn J Pharmacol. 1977 Feb;27(1):97-103. doi: 10.1254/jjp.27.97.
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.
比较了几种抑制剂对来自不同器官的环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）磷酸二酯酶的抑制常数。这些抑制剂包括经典的茶碱、罂粟碱以及一些新开发的抑制剂：一种咪唑烷酮化合物RO20 - 1724，以及两种酞嗪醇化合物EG 467和EG 626。在所测试的抑制剂中，罂粟碱和EG 626被发现是最有效的。这两种化合物对血小板和动脉磷酸二酯酶具有极强的抑制作用。在血小板提取物和脑提取物中，EG 626对cAMP磷酸二酯酶的抑制作用比对cGMP磷酸二酯酶的抑制作用强得多，而RO20 - 1724在脑提取物中对cAMP磷酸二酯酶有抑制作用，但对cGMP磷酸二酯酶无抑制作用。当皮肤腺苷酸环化酶被AMP激活时，加入茶碱会阻断这种激活，但EG 626或EG 467会进一步增强这种激活作用。这些体外研究可作为特定磷酸二酯酶抑制剂有效性的基础筛选试验。
