Disease relevance of nifekalant

• OBJECTIVES: We tested whether a new class III drug (MS-551) administered during ventricular fibrillation (VF) could decrease the defibrillation threshold (DFT) in anesthetized canine hearts [1].
• We then compared the DFTs after 130 s of VF with and without administration of MS-551 (2 mg/kg body weight) at 10 s after the onset of VF in 12 open chest dogs and 8 closed chest dogs [1].
• MS-551 induced arrhythmias in five out of seven dogs (TdP in one dog) [2].
• During the 30 min of MS-551 infusion, arrhythmias occurred in three out of seven dogs (torsades de pointes (TdP) type VT in one dog) [2].
• However, repeated administration of MS-551 protected against sudden cardiac death in 8 of 10 dogs as compared with 2 of 12 in the vehicle-treated group (p < 0.05) [3].

High impact information on nifekalant

• OBJECTIVE: The frequency-dependent effects of MS-551 on the action potential duration (APD) and the underlying ionic mechanisms were investigated in comparison with those of E-4031 [4].
• MS-551 infusion, 1 mg/kg/30 min, decreased the heart rate (HR) by 16% (P<0.01) and prolonged the QTc interval by 20% (P<0.01) [2].
• In conclusion, MS-551 is a potent class III antiarrhythmic agent that selectively prolongs repolarization in the ventricular myocardium and appears to be devoid of autonomic effects [5].
• Also in the propranolol pre-treated dogs, MS-551 induced arrhythmias in five out of seven dogs (TdP in 1 dog) [2].
• We investigated the proarrhythmic effects of MS-551 and KCB-328, class III antiarrhythmic drugs using adrenaline-induced arrhythmia models in halothane anaesthetized, closed-chest dogs [2].

Chemical compound and disease context of nifekalant

• The PES induced arrhythmias are thought to be induced exclusively by a reentrant mechanism, but the reperfusion arrhythmias may involve not only re-entry, but also automaticity, and we reported the effectiveness of MS-551, E-4031 and d-sotalol on the latter arrhythmia [6].
• The purpose of this study was to assess the electrophysiologic properties and anti-arrhythmic efficacy for inducible sustained ventricular tachycardias (VTs) of the pure class III agent nifekalant hydrochloride (MS-551) in comparison with those of procainamide [7].
• Effects of class Ic drug pilsicainide and class III drug MS-551 were determined in the canine model of atrial fibrillation (AF) induced under vagal stimulation [8].
• Nifekalant hydrochloride (MS-551), a pure K(+) channel blocker, might be effective for postoperative recurrent ventricular tachyarrhythmias that are refractory to other antiarrhythmic agents [9].

Biological context of nifekalant

• Effects of MS-551, a new class III antiarrhythmic drug, on programmed stimulation-induced ventricular arrhythmias, electrophysiology, and hemodynamics in a canine myocardial infarction model [10].
• MS-551 at either low or high dose did not significantly change the heart rate (HR), mean blood pressure (MBP), cardiac output (CO), or maximum rate of increase in left ventricular pressure (LVP) significantly [10].

Anatomical context of nifekalant

• Effects of MS-551, a new class III antiarrhythmic drug, on action potential and membrane currents in rabbit ventricular myocytes [11].
• The inhibition constant (Ki) for MS-551 in glandular membranes was also slightly greater than the high-affinity Ki value for the drug in atrial membranes [12].
• Inhibition of ATP-sensitive potassium channels in cardiac myocytes by the novel class III antiarrhythmic agent MS-551 [13].

Associations of nifekalant with other chemical compounds

• IK independent class III actions of MS-551 compared with sematilide and dofetilide during reperfusion in anaesthetized rats [14].
• Although the competition curve of D,L-sotalol for [3H]-NMS binding to atrial membranes was monophasic, that of MS-551 was biphasic and showed high- and low-affinity states of binding [12].

Gene context of nifekalant

• A new class III antiarrhythmic drug, MS-551, blocks the inward rectifier potassium channel in isolated guinea pig ventricular myocytes [15].

Analytical, diagnostic and therapeutic context of nifekalant

• 5. In conclusion, in rats which are deficient in cardiac IK MS-551 prolonged the QT interval and reduced the incidence of sustained VF after reperfusion [14].
• However, 10 mg kg-1 MS-551 delayed the onset of reperfusion-induced VF (27 +/- 5 s compared with 12 +/- 2 s of the control group, P < 0.05) [14].
• 2. Before coronary ligation, 3 and 10 mg kg-1 MS-551 decreased the heart rate by 6% (P < 0.01) and 12% (P < 0.01), and increased mean arterial pressure (MAP) by 14% (P < 0.05) and 33% (P < 0.01), respectively [14].
• 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 [16].
• 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 [16].

References