新型钙拮抗药LR-A/113的抗心律失常作用

Antiarrhythmic effects of LR-A/113 a new calcium antagonistic drug.

作者信息

Stella L, de Novellis V, Vacca C, Guarino A, Cantoni V, Fici F, Rossi F

机构信息

Institute of Pharmacology and Toxicology Faculty of Medicine, University of Naples, Italy.

出版信息

Res Commun Mol Pathol Pharmacol. 1996 Aug;93(2):235-48.

PMID:8884994

Abstract

LR-A/113 is a benzothiazepine drug similar to diltiazem with Ca(2+)-antagonist properties. Our previous studies showed that LR-A/113 determines anthypertensive effects comparable to diltiazem in normotensive and hypertensive rats. The aim of this study is to determine LR-A/113 effects respect to verapamil and diltiazem on CaCl2, aconitine and ouabain arrhythmias. Experiments were carried out on normotensive anesthetized rats and guinea pigs treated with CaCl2, aconitine and ouabaine and pretreated or not with verapamil, diltiazem or LR-A/113. Verapamil, diltiazem and LR-A/113, significantly delayed onset of arrhythmias and cardiac standstill induced by CaCl2 and aconitine. Moreover, pretreatments with verapamil, diltiazem or LR-A/113 reduced occurrence of arrhythmias in animals. In our models of arrhythmias LR-A/113 showed a significant antiarrhythmic effect of a magnitude almost similar to diltiazem but lower than for verapamil.

摘要

LR-A/113是一种苯并硫氮䓬类药物，与地尔硫䓬类似，具有钙（2+）拮抗剂特性。我们之前的研究表明，LR-A/113在正常血压和高血压大鼠中产生的降压效果与地尔硫䓬相当。本研究的目的是确定LR-A/113相对于维拉帕米和地尔硫䓬对氯化钙、乌头碱和哇巴因所致心律失常的影响。实验在正常血压的麻醉大鼠和豚鼠身上进行，这些动物用氯化钙、乌头碱和哇巴因处理，并预先用或不用维拉帕米、地尔硫䓬或LR-A/113进行预处理。维拉帕米、地尔硫䓬和LR-A/113显著延迟了氯化钙和乌头碱所致心律失常的发作以及心脏停搏。此外，用维拉帕米、地尔硫䓬或LR-A/113预处理可减少动物心律失常的发生。在我们的心律失常模型中，LR-A/113显示出显著的抗心律失常作用，其程度几乎与地尔硫䓬相似，但低于维拉帕米。