Separation of the Coronary Vasodilator from the Cardiac Effects of PN 200–110, a New Dihydropyridine Calcium Antagonist, in the Dog Heart

Coronary vasodilator and cardiac effects of PN 200–110 were compared by use of isolated, blood-perfused sinoatrial (SA) node. atrioventrieular (AV) node, and papillary muscle preparations of dogs. (PN) 200–110 was administered intraarterially. In all preparations PN 200–110 produced an increase in coronary blood flow. In SA node preparations, the drug produced a decrease in sinus rate and atrial standstill as well, but only in large doses. The dose that produced a 15% cnearly half-maximuml decrease in sinus rate was about three times the dose that doubled coronary blood How. In AV node preparations, the drug produced an increase in AV conduction time and. in large doses, second- or third-degree AV block only when it was injected into the artery supplying the AV node. The dose that produced a 15% (nearly half-maximum) increase in AV conduction time was 12 times the dose that doubled coronary blood flow. In paced papillary1 muscle preparations, the drug produced a decrease in the force of contraction. However, the close that produced a 50% decrease in the force of contraction of the papillary muscle was 14 limes the dose that doubled coronary blood flow. These effects of PN 200–110 were of long duration. The drug was entirely ineffective in changing the rate of ventricular automaticity. The order of selectivity of PN 200–110 was as follows: coronary blood flow SA nodal automaticity AV nodal conduction ventricular muscle contraction. This cardiovascular profile of PN 200–110 is slightly different from that of PY 108–068. a compound closely related to PN 200–110 in chemical structure.