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.
Yoshioka
K
K
Research Laboratory, Zenyaku Kogyo Co., Ltd., Tokyo, Japan.
Hino
M
M
Yoshimura
A
A
Yamazaki
H
H
Takase
M
M
Ono
H
H
D000818:Animals; D002316:Cardiotonic Agents; D002415:Cats; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010424:Pentobarbital / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology*
D002316:Cardiotonic Agents; D011728:Pyridones; D013843:Thiazines; C050142:ZSY 27; D011433:Propranolol; D010424:Pentobarbital; D020105:Milrinone