Inotropic versus chronotropic, dromotropic, and coronary vasodilator actions of DPI 201-106, a novel positive inotropic agent, in the dog heart.
Inotropic versus chronotropic, dromotropic, and vascular effects of DPI 201-106 were assessed in isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. DPI 201-106 was administered intraarterially. In paced papillary muscles the drug produced an increase in developed tension. In spontaneously beating papillary muscles the drug slightly decreased the beating rate. In SA node preparations the drug decreased sinus rate, and atrial standstill ensued from the highest dose. In AV node preparations the drug affected AV conduction only when administered into the AV node artery, and in high doses second- or third-degree AV block occurred. In all preparations the drug increased blood flow. DPI 201-106 at the dose that produced a 50% increase in the force of contraction of ventricular muscle increased coronary blood flow by 8.4%, AV conduction time by 7.6%, and decreased sinus rate by 2.6%, indicating its high selectivity for force. When infused into the AV node artery, the drug in high doses produced dose-dependent prolongations of both the AV nodal conduction time and the functional refractory period of the AV node, which were pronounced with elevation of the pacing rate. These effects of DPI 201-106 are very similar to those of calcium channel blockers.
D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D014665:Vasodilator Agents
D010879:Piperazines; D014665:Vasodilator Agents; C046261:DPI 201-106