Cardiovascular effects of OPC-13340, a potent, long-acting 1,4-dihydropyridine calcium channel blocker, in dogs.
The cardiovascular effects of OPC-13340, a newly developed 1,4-dihydropyridine calcium channel blocker, were examined in several canine preparations. In conscious normotensive and DOCA-salt hypertensive dogs, OPC-13340, at doses of 10 to 30 micrograms/kg, i.v., and 0.3 to 3 mg/kg, p.o., exerted an hypotensive action in a dose-dependent manner. The hypotensive action of OPC-13340 was longer lasting and more potent than that of nicardipine and nifedipine. In conscious, normotensive instrumented dogs, OPC-13340, at doses of 1 and 3 mg/kg, p.o., dose-dependently decreased total peripheral resistance and mean blood pressure and increased heart rate, cardiac output and left ventricular contractility. In anesthetized open-chest dogs, OPC-13340, at doses of 1 to 30 micrograms/kg, i.v., increased coronary blood flow and decreased mean blood pressure, heart rate, coronary vascular resistance, arteriovenous oxygen difference and myocardial oxygen consumption. In contrast to OPC-13340, nicardipine did not change the myocardial oxygen consumption. From these results it was concluded that OPC-13340 lowered blood pressure and improved coronary circulation in dogs and that the duration of these actions was longer lasting than that of nifedipine and nicardipine. These actions of OPC-13340 may be useful in the treatment of hypertension and angina pectoris.
Mori
T
T
2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co. Ltd., Japan.
Nakayama
N
N
Ohura
M
M
Ikezono
K
K
Kinoshita
S
S
Kamata
M
M
Hosokawa
T
T
Yamashita
S
S
Yabuuchi
Y
Y
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003900:Desoxycorticosterone; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D003900:Desoxycorticosterone; C048161:pranidipine; D009529:Nicardipine; D009543:Nifedipine