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.