We compared the coronary
vasodilator and cardiac effects of
MCI-176, a novel
quinazolinone calcium antagonist, in isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. The
drug was administered intraarterially. In SA node preparations
MCI-176 reduced sinus rate and produced atrial standstill in large doses. In AV node preparations
MCI-176 prolonged AV conduction time and produced second- or third-degree
AV block in large doses only when administered into the artery supplying the AV node, but failed to affect AV conduction when administered into the artery supplying the His-Purkinje-ventricular system. In paced papillary muscle preparations
MCI-176 reduced the force of contraction. In spontaneously beating papillary muscles
MCI-176 failed to change the beating rate.
MCI-176 increased blood flow in all preparations. The dose that doubled blood flow was slightly larger than the dose that produced a 15% increase in AV conduction time, but about one-third the dose that produced a 15% decrease in sinus rate. The dose estimated to reduce the force of contraction by half was more than approximately 10 times the dose that doubled blood flow. The results indicate that
MCI-176 can be classified as a nonvasoselective
calcium antagonist but that it differs from others.