A comparative study of the pharmacodynamic effects of nimodipine and nifedipine in the isolated spontaneously beating rabbit heart.
Myocardial effects of the calcium antagonistic drugs nimodipine and nifedipine were comparatively studied in retrogradely perfused rabbit hearts at stepwise increasing drug concentrations in the perfusion liquid within the range of 1-60 ng ml-1. Pharmacodynamic steady states developed slowly within about 25 min. at each concentration level. Nimodipine produced in comparison with nifedipine a progressive and very marked negative chronotropic effect and caused simultaneously a very pronounced increase in the QT-interval. The potency of nimodipine with regard to these effects were about 10 times that of nifedipine. The PQ-interval was only increased significantly at the two highest concentrations of nimodipine. Both drugs caused a pronounced inhibition of myocardial contractility as judged from the decrease in contraction amplitude and rate of contraction. Myocardial efficiency expressed as the ratio of contraction-rate to oxygen consumption decreased progressively and highly significantly with increasing drug concentrations. The relative potency between nimodipine and nifedipine with regard to the negative inotropic effects was only about 1.7. Increasing exposure to nimodipine produced a progressive decrease of the mean coronary flow-rate, whereas nifedipine initially caused an increase followed by a terminal decrease to the initial flow-rate level.
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003864:Depression, Chemical; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009539:Nicotinic Acids / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology*; D009553:Nimodipine; D010101:Oxygen Consumption / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits
D009539:Nicotinic Acids; D011725:Pyridines; D009553:Nimodipine; D009543:Nifedipine