THE STRUCTURALLY NOVEL CA-2+ CHANNEL BLOCKER RO 40-5967, WHICH BINDS TO THE [H-3] DESMETHOXYVERAPAMIL RECEPTOR, IS DEVOID OF THE NEGATIVE INOTROPIC EFFECTS OF VERAPAMIL IN NORMAL AND FAILING RAT HEARTS

被引：85

作者：

CLOZEL, JP

VENIANT, M

OSTERRIEDER, W

机构：

[1] Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd, Basel

来源：

CARDIOVASCULAR DRUGS AND THERAPY | 1990年 / 4卷 / 03期

关键词：

calcium antagonists; heart failure; myocardial contractility; Ro; 40-5967; verapamil;

D O I：

10.1007/BF01856562

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Ro 40-5967 is a structurally novel Ca2+ channel blocker that binds to the verapamil-type receptor of cardiac membranes but that has been shown in isolated guinea-pig hearts to be about ten times less potent a negative inotropic agent than verapamil. The goals of the present study were to confirm these findings in vitro in isolated perfused rat hearts as well as in vivo in conscious rats and to compare Ro 40-5967 to verapamil. The effects of Ro 40-5967 and verapamil were tested not only in normal rats, but also in rats with heart failure induced by chronic myocardial infarction. In isolated Langendorff hearts (without heart failure), no decrease of contractility was observed with Ro 40-5967 up to complete AV block. In contrast, verapamil decreased contractility with an IC50 of 100 nM. In isolated, electrically stimulated rat papillary muscles, the IC50 values for the decrease of contractile force were 15,000 and 440 nM for Ro 40-5967 and verapamil, respectively. In vivo, Ro 40-5967 did not decrease left ventricular contractility (as assessed by changes of dP/dt max+) in rats without and with heart failure. In contrast, verapamil was markedly negative inotropic in both conditions. © 1990 Kluwer Academic Publishers.

引用

页码：731 / 736

页数：6

共 16 条

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