The cardiovascular effects of
ZSY-39 [4-methyl-5-(4-pyridinyl)-
thiazole-2-carboxyamide] were investigated in isolated and blood-perfused atrial and ventricular muscles perfused with donor's arterial blood. When
ZSY-39 was given i.v. to the intact donor dog,
hypotension with a slight
tachycardia was induced at a dose range of 30-1,000 micrograms/kg. At the same time, slight positive chronotropic and inotropic responses appeared in isolated, perfused atria at i.v. doses of 300 and 1,000 micrograms/kg
ZSY-39, indicating a relatively dominant inotropic action. Direct injection of
ZSY-39 into the cannulated sinus node artery of the isolated atrium produced positive chronotropic and inotropic responses in a dose-related manner (1 to 300 micrograms).
ZSY-39 also induced a dose-dependent increase in developed tension in the isolated ventricle. The positive chronotropic and inotropic effects of
ZSY-39 were not modified by an adequate dose of
propranolol which completely blocked
norepinephrine-induced positive chronotropic and inotropic responses. From these results, it is concluded that
ZSY-39 has mild
cardiotonic properties, showing relatively selective positive inotropic activity.