Oizumi K, Koike H, Sada T, Miyamoto M, Nishino H, Matsushita Y, Iijima Y, Yanagisawa H
Sankyo Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Jpn J Pharmacol. 1988 Nov;48(3):349-56. doi: 10.1254/jjp.48.349.
CS-622 is a prodrug type ACE inhibitor with a thiazepin ring. Its active form, CS-622 diacid, was slightly more potent than enalaprilat in inhibiting ACE isolated from rabbit lung. The inhibitory potency of CS-622 diacid on isolated rat aorta was 3 times that of enalaprilat. The inhibitory action of enalaprilat was abolished quickly by washing the aortic strip with drug-free solution, whereas that of CS-622 diacid was abolished only slowly. This difference suggests that CS-622 diacid binds to vascular ACE more firmly than enalaprilat. By oral administration, CS-622 was 3 times more potent than enalapril, and its onset of action was faster than that of enalapril, suggesting that the conversion of CS-622 to its active diacid occurs faster than the conversion of enalapril. Although CS-622 diacid was only slightly more potent than enalaprilat by intravenous administration, it had a longer duration than enalaprilat. Elimination of renal excretory function potentiated the action of captopril but not that of CS-622, suggesting that unlike captopril, only a small portion of CS-622 is excreted through the kidney.
CS - 622是一种带有噻氮平环的前体药物型血管紧张素转换酶（ACE）抑制剂。其活性形式CS - 622二酸在抑制从兔肺中分离出的ACE方面比依那普利拉略强。CS - 622二酸对离体大鼠主动脉的抑制效力是依那普利拉的3倍。用无药溶液冲洗主动脉条可迅速消除依那普利拉的抑制作用，而CS - 622二酸的抑制作用只能缓慢消除。这种差异表明CS - 622二酸比依那普利拉更牢固地结合于血管ACE。口服给药时，CS - 622的效力是依那普利的3倍，且其起效比依那普利更快，这表明CS - 622向其活性二酸的转化比依那普利更快。虽然静脉给药时CS - 622二酸仅比依那普利拉略强，但其作用持续时间比依那普利拉更长。消除肾脏排泄功能可增强卡托普利的作用，但对CS - 622无效，这表明与卡托普利不同，只有一小部分CS - 622通过肾脏排泄。
