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.

[1]  Y. Imai,et al.  PHARMACOLOGICAL PROFILE OF A NEW CORONARY VASODILATOR DRUG, 2‐NICOTINAMIDOETHYL NITRATE (SG‐75) , 1979, Clinical and experimental pharmacology & physiology.

[2]  M. Lièvre,et al.  RELATIONSHIP BETWEEN ATRIAL AND VENTRICULAR RATES OF FIBRILLATION AND CARDIAC CONTRACTILE TISSUE EFFECTIVE REFRACTORY PERIODS IN THE DOG , 1978, British Journal of Pharmacology.

[3]  A. L. Wit,et al.  The Effects of Acetylcholine on the Electrical Activity of Canine Cardiac Purkinje Fibers , 1978, Circulation research.

[4]  Y. Uchida,et al.  Effect of 2-nicotinamidethyl nitrate (SG 75) on coronary circulation. , 1978, Japanese heart journal.

[5]  T. Yanagisawa,et al.  Effects on atrio-ventricular conduction of propranolol, pindolol and carteolol in the dog heart in situ as assessed by automated devices. , 1978, Japanese Journal of Pharmacology.

[6]  A. Fleckenstein.  Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. , 1977, Annual review of pharmacology and toxicology.

[7]  N. Taira,et al.  Simultaneous assessment of effects of coronary vasodilators on the coronary blood flow and the myocardial contractility by using the blood-perfused canine papillary muscle. , 1976, Japanese journal of pharmacology.

[8]  J. Han,et al.  Effect of acetylcholine on automaticity of canine Purkinje fibers. , 1976, The American journal of physiology.

[9]  R. Tsien,et al.  Effects of Epinephrine on the Pacemaker Potassium Current of Cardiac Purkinje Fibers , 1974, The Journal of general physiology.

[10]  T. Kimura,et al.  Effect of manganese ions on the contraction and automaticity of the blood-perfused canine papillary muscle. , 1974, Japanese Journal of Pharmacology.

[11]  R. Charlier.  Antianginal Drugs: Pathophysiological, Haemodynamic, Methodological, Pharmacological, Biochemical and Clinical Basis for Their Use in Human Therapeutics , 1971 .

[12]  K. Hashimoto,et al.  Pharmacological evidence of autonomic nerve activities in canine papillary muscle. , 1970, The American journal of physiology.

[13]  G. W. Beeler,et al.  The relation between membrane potential, membrane currents and activation of contraction in ventricular myocardial fibres , 1970, The Journal of physiology.

[14]  B. Hoffman,et al.  Cardiac cellular potentials; effect of vagal stimulation and acetylcholine. , 1953, The American journal of physiology.

[15]  L. Katz,et al.  The Mechanism of Auricular Flutter and Auricular Fibrillation , 1953 .