Cardiovascular effects of ZSY-27 [5-methyl-6-(4-pyridinyl)-2H-1,4-thiazine-3(4H)-one X hydrochloride] in the dog cross-circulated atrial preparation.

Abstract

A new cardiotonic compound, 5-methyl-6-(4-pyridinyl)-2H-1,4-thiazine-3(4H)-one X hydrochloride (ZSY-27), was investigated in cross-circulated dog atrial muscle preparations. When ZSY-27 was intravenously administered to the donor dog, a dose-dependent depressor effect with slight sinus tachycardia was induced in the donor dog. At the same time, a significant dose-dependent increase in developed tension was usually observed in an isolated atrium perfused with donor's arterial blood, but there were no significant changes in sinus cycle length and sinoatrial conduction time. The ZSY-27-induced positive inotropic effect was not significantly influenced by treatment with propranolol in doses which completely inhibited norepinephrine-induced positive chronotropic and inotropic effects. When ZSY-27 was injected into the cannulated sinus node artery of the isolated atrium, dose dependent positive chronotropic and inotropic effects were induced. The dominant increases in developed tension by ZSY-27 were similar to effects of other phosphodiesterase inhibitors, such as papaverine and aminophylline. From these results, it is concluded that ZSY-27 has non-adrenergic, cardiotonic properties with a depressor effect.