Circumstantial evidence for increased potassium conductance of membrane of cardiac muscle by 2-nicotinamidoethyl nitrate (SG-75).
The mechanism of action of 2-nicotinamidoethyl nitrate (SG-75), was investigated by the use of arterially blood-perfused papillary muscle preparations of the dog. All drugs were administered intra-arterially. SG-75 shortened the effective refractory period (ERP) and decreased the rate of automaticity and developed tension of the papillary muscle, whereas verapamil failed to change the ERP despite a decrease in the developed tension. SG-75 in extremely high doses induced ventricular fibrillation. Methacholine produced decreases in the rate of automaticity and developed tension, and the actions were abolished by atropine. The SG-75-induced decreases in two parameters were not modified by atropine. These results indicate that the cardiac action of SG-75 differs from that of calcium-antagonistic vasodilators and it is suggested that the basic mechanism of action of SG-75 involves an increase in potassium conductance in the membrane of cardiac muscle, without mediation through muscarinic receptors.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003864:Depression, Chemical; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008688:Methacholine Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D009566:Nitrates / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects*; D010477:Perfusion; D011188:Potassium / Q000502:physiology*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D014693:Ventricular Fibrillation / Q000139:chemically induced; D014700:Verapamil / Q000494:pharmacology
D008688:Methacholine Compounds; D009566:Nitrates; D009536:Niacinamide; D020108:Nicorandil; D001285:Atropine; D014700:Verapamil; D011188:Potassium