Chronotropic, inotropic, and vasodilator actions of diltiazem, nifedipine, and verapamil. A comparative study of physiological responses and membrane receptor activity.

摘要: The three major, chemically distinct calcium channel-blocking drugs, diltiazem, nifedipine, and verapamil, produce coronary vasodilation in the conscious dog. Coronary vascular resistance was reduced by 50% with an intravenous dose of 3 micrograms/kg 30 100 diltiazem. In dogs, nifedipine verapamil increased heart rate, whereas diltiazem produced a smaller increase rate. rate left ventricular pressure development dogs unaffected decreased verapamil. Tachycardia reversed to bradycardia consistent negative inotropic effects were demonstrated all drugs only after combined autonomic blockade atropine propranolol dogs. isolated dog artery strips contracted ex vivo 50 mM potassium chloride, ID50 for relaxation 0.01 microM 0.02 0.30 hearts, agents dose-dependent chronotropy 25% reduction spontaneous achieved 0.09 0.20 0.40 Similarly, force myocardial depressed 0.03 microM; 0.10 microM. On membrane level, interacted putative receptor or site associated channel specifically labelled [3H]nimodipine. specific binding cardiac sarcolemma competitively inhibited partly stimulated but not effect occurred at pharmacologically active concentrations. Considerable nonspecific dihydropyridines may account, least part, discrepancies between their dissociation constants on purified ED50 pharmacological effects. Diltiazem (1 microM) did alter [3H]nimodipine binding. These results strongly suggest that have different sites action.