Cardiotonic activity of 5-methyl-6-(4-pyridyl)-2H-1,4-thiazin-3(4H)-one hydrochloride (ZSY-27).

Cardiotonic activity of a new, non-catecholamine and non-glycoside positive inotropic agent, 5-methyl-6-(4-pyridyl)-2H-1,4-thiazin-3(4H)-one hydrochloride (ZSY-27), was investigated in isolated guinea pig left atria, cat right ventricular papillary muscle and cross-circulated excised dog papillary muscle preparations, and in anesthetized open-chest dogs. In electrically driven guinea pig left atria and cat papillary muscle preparations, ZSY-27 (3 x 10(-6)-10(-4) M) increased the developed tension in a concentration-related manner. The positive inotropic effect of ZSY-27 was not blocked by propranolol (3 x 10(-8) M) in the guinea pig atria, but was significantly inhibited by carbachol (5 x 10(-6) M) in cat papillary muscle preparations. The positive inotropic effect of ZSY-27 was comparable to that of milrinone in guinea pig atria. ZSY-27 (0.01-3 mg) increased dose-dependently the developed tension in cross-circulated excised dog papillary muscle preparations as well. In anesthetized dogs, ZSY-27 (0.03-1 mg/kg, i.v.) produced a dose-dependent increase in left ventricular contractile force and a decrease in blood pressure, while the increase in heart rate was relatively small. The pharmacological profile of ZSY-27 in anesthetized dogs was similar to that of milrinone. These results suggest that ZSY-27 is potent cardiotonic agent with vasodilator activity and its effect may be partially due to an increase in the intracellular adenosine 3',5'-cyclic monophosphate level.