Antiarrhythmic Effects of MS-551, a New Class III Antiarrhythmic Agent, on Canine Models of Ventricular Arrhythmia.

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概要

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• -The antiarrhythmic effects of MS-551, which prolongs cardiac action potential duration without affecting the maximum upstroke velocity of the action potential, were assessed in three different canine ventricular arrhythmia models: 1) ventricular tachycardia (VT) induced by electrical stimuli 3-5 days after myocardial infarction, 2) spontaneous ventricular tachyarrhythmias 24-48 hr after two-stage coronary ligation and 3) ventricular tachyarrhythmias induced by digitalis. Intravenous administration of MS-551 (0.1-1 mg/kg) decreased the susceptibility in 10 dogs out of 13 to VT or ventricular fibrillation evoked by programmed electrical stimulation (PES) delivered to the ventricular septum 3-5 days after myocardial infarction. Oral administration of MS-551 (3 mg/kg) also decreased the susceptibility to VT evoked by PES in 7 out of 10 conscious postinfarction dogs. Concurrently, intravenous (0.1-1 mg/kg) or oral (3 mg/kg) administration of MS-551 produced increases in the ventricular effective refractory periods (ERP) by 7 ± 1%-17 ± 3% or 13 ± 2%, respectively. Similarly, <I>d</I>-sotalol (0.3-3 mg/kg, i.v. and 10 mg/kg, p.o.) decreased the susceptibility to VT with increased ERP. However, MS-551 (1 and 10 mg/kg, i.v.) failed to inhibit both canine two-stage coronary ligation arrhythmia and digitalis arrhythmia. These results suggest that MS-551 is a pure class III antiarrhythmic drug which may be effective in the treatment of life-threatening reentrant tachyarrhythmias, but not in automaticity arrhythmias.

• 公益社団法人 日本薬理学会の論文

著者

• KAMIYA Joji

  Department of Pharmacology, Niigata University, School of Medicine

• ISHII Masaaki

  Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, The University of

• Katakami Tsutomu

  Life Science Laboratory, Central Research Institute, Mitsui Toatsu Chemicals, Inc.

• Ishii Masaaki

  Department of Pharmacology, Institute of Biological Science, Mitsui Pharmaceuticals, Inc.

• Kamiya Joji

  Department of Pharmacology, Institute of Biological Science, Mitsui Pharmaceuticals, Inc.

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• Antiarrhythmic Effects of MS-551, a New Class III Antiarrhythmic Agent, on Canine Models of Ventricular Arrhythmia.
• Effect of cibenzoline, a class I antiarrhythmic drug, on action potential in canine ventricular muscle.
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