title: Pharmacological profiles of CS-622, a novel angiotensin converting enzyme inhibitor.
abstract: 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.
authors.affiliation: Sankyo Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Oizumi
authors.forename: H
authors.initials: H
authors.lastname: Koike
authors.forename: T
authors.initials: T
authors.lastname: Sada
authors.forename: M
authors.initials: M
authors.lastname: Miyamoto
authors.forename: H
authors.initials: H
authors.lastname: Nishino
authors.forename: Y
authors.initials: Y
authors.lastname: Matsushita
authors.forename: Y
authors.initials: Y
authors.lastname: Iijima
authors.forename: H
authors.initials: H
authors.lastname: Yanagisawa
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D015773:Enalaprilat; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011355:Prodrugs; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013841:Thiazepines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D011355:Prodrugs; D013841:Thiazepines; D004656:Enalapril; C055603:temocapril hydrochloride; D015773:Enalaprilat