Comparison of coronary dilating effects of Ki1769, a new K channel opener of the pyridinecarboximidamide type, and nifedipine in anesthetized dogs.
The coronary dilating effect of a new type of K channel opener, N-cyano-N'-(2-phenethyl)-3-pyridinecarboximidamide (Ki1769), was examined in anesthetized dogs in comparison with that of nifedipine. Administration of Ki1769 (30 and 100 micrograms/kg, i.v.) and nifedipine (1 and 3 micrograms/kg, i.v.) produced a dose-dependent decrease of mean blood pressure with a concomitant increase in heart rate. Ki1769 and nifedipine dose-dependently increased coronary blood flow and aortic blood flow and decreased coronary vascular resistance and total peripheral vascular resistance. The percentage decrease of coronary vascular resistance was greater than that of total peripheral vascular resistance with Ki1769 and nifedipine, but Ki1769 showed a greater specificity in the decrease of coronary vascular resistance than nifedipine. Glibenclamide (5 mg/kg, i.v.) inhibited these hemodynamic effects of Ki1769 but did not affect those of nifedipine. These results suggest that the preferential effect of Ki1769 on the coronary vascular bed is greater than that of nifedipine. Such a profile of Ki1769 is based on its K channel-opening action.
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
T
T
Yokoyama
S
S
Kaneta
A
A
Miwa
Y
Y
Tanaka
H
H
Izumi
T
T
Izawa
N
N
Ogawa
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D015220:Calcium Channels; D015221:Potassium Channels; D011725:Pyridines; D014665:Vasodilator Agents; C084622:Ki 1769; D009543:Nifedipine