Cardiovascular pharmacological studies on JTV-506, a new potassium channel opener. 2nd communication: effects on blood pressure in conscious animals.
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 blood pressure were evaluated in conscious dogs and rats. In conscious dogs, JTV-506 (0.01-1 mg/kg p.o.), levcromakalim (0.01-1 mg/kg p.o.) and nifedipine (3-30 mg/kg p.o.) elicited an increase in double product, whereas nicorandil (1-10 mg/kg p.o.) did not affect the double product. The JTV-506-induced increase in double product was abolished by a beta-blocker, propranolol, suggesting that this increase in double product may be due to augumentation of heart rate by sympathetic nerves which mediate the baroreflex. The doses at which JTV-506 increased coronary blood flow in a previous study were lower than the doses required to increase the double product. JTV-506 did not have a crucial influence on electrocardiogram. In conscious rats, orally administered JTV-506, levcromakalim, nicorandil and nifedipine reduced blood pressure and increased heart rate dose dependently. These effects were more remarkable in hypertensive rats than in normotensive rats. JTV-506, a new potassium channel opener, seems to be relatively free of any hemodynamic effects.
Hirata
Y
Y
Biological/Pharmacological Research Laboratories, Japan Tobacco, Inc., Takatsuki, Japan.
Suzuki
Y
Y
Miyai
H
H
Aisaka
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology*; D003243:Consciousness / Q000502:physiology; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D015221:Potassium Channels / Q000819:agonists*; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002839:Chromans; C107494:JTV 506; D015221:Potassium Channels; D014665:Vasodilator Agents