Cardiovascular pharmacological studies on JTV-506, a new potassium channel opener. 1st communication: effects on myocardium and vasculature.
The effects of JTV-506 ((-)-(3S,4R)-2,2-bis(methoxymethyl)-4-[(1,6-dihydro-1-methyl-6-oxo-3- pyridazinyl)amino]-3-hydroxychroman-6-carbonitrile hemihydrate, CAS 170148-29-5), a novel coronary vasodilator, on hemodynamics, cardiac function and cardiac oxygen consumption were evaluated in anesthetized dogs. In anesthetized, open-chest dogs, JTV-506 (0.3-10 micrograms/kg i.v.) induced a marked increase in coronary blood flow in a dose dependent manner, while at these doses it had smaller effects on vertebral and mesenteric blood flow and almost no effect on renal blood flow. JTV-506 (1-10 micrograms/kg i.v.) showed a tendency to decrease oxygen consumption of the heart and elevate myocardial oxygen pressure without cardiac suppression. Effects of JTV-506 on hemodynamics and the respiratory system following i.v. administration (0.3-300 micrograms/kg) were investigated in spontaneously breathing anesthetized dogs. The effective dose to induce hemodynamic changes was more than 3 micrograms/kg. JTV-506 did not have a crucial influence on electrocardiogram. JTV-506 caused marked increase in coronary blood flow and myocardial oxygen pressure with slight change in blood pressure. It is concluded that JTV-506 is a potent vasodilator, with particularly pronounced effect on vasculature of the heart. These results suggest that JTV-506 may be useful in the treatment of angina pectoris.
Hirata
Y
Y
Biological/Pharmacological Research Laboratories, Japan Tobacco Inc., Takatsuki, Japan.
Suzuki
Y
Y
Miyai
H
H
Aisaka
K
K
D000758:Anesthesia; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D015221:Potassium Channels / Q000819:agonists*; D012077:Renal Artery / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D014711:Vertebral Artery / Q000187:drug effects
D002839:Chromans; C107494:JTV 506; D015221:Potassium Channels; D014665:Vasodilator Agents