Cardiovascular profile of MPC-1304, a novel dihydropyridine calcium antagonist: comparison with other calcium antagonists.
The cardiovascular profile of a novel calcium antagonist, MPC-1304 and its active metabolites were investigated in experimental animals in vitro and in vivo, and were compared with those of other calcium antagonists or nitroglycerin (NTG). The ratio of negative chronotropic/negative inotropic effect of MPC-1304 was 23 times higher than that of nifedipine in paced left and spontaneously beating right atria of guinea pigs. MPC-1304 and nifedipine did not change atrial-His (AH) conduction time or His-ventricular (HV) conduction time at hypotensive doses in open-chest dogs, whereas diltiazem prolonged AH time. MPC-1304 increased coronary blood flow, and strongly decreased myocardial oxygen consumption (MVO2) by decreasing blood pressure (BP) and heart rate (HR) in open-chest dogs. Left ventricular pressure (LVP) was not changed. Contractile force (dp/dt) was slightly increased by its action on afterload. MPC-1304 and nifedipine did not dilate the large coronary artery, but NTG did. MPC-1304 increased blood flow of the peripheral arteries, especially vertebral and CBF in anesthetized dogs. Cerebral blood flow (CBF) also increased. MPC-1304 decreased serum cholesterol levels and the plaque area of the aorta in cholesterol-fed rabbits. Because of this cardiovascular profile, MPC-1304 should be useful in treatment of hypertension as well as angina pectoris.
Kanda
A
A
Pharmacology Research Laboratory, Taiho Pharmaceutical, Tokushima, Japan.
Haruno
A
A
Miyoshi
K
K
Tanahashi
Y
Y
Miyake
H
H
Ichihara
K
K
Okumura
K
K
Nagasaka
M
M
D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control; D001283:Atrioventricular Node / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002319:Cardiovascular System / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011817:Rabbits
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C059427:aranidipine