Disease relevance of Pilsicainide

• OBJECTIVES: The purposes of this study were to measure the atrial refractory period and the conduction velocity (CV) during atrial fibrillation (AF) and to explore the antiarrhythmic mechanism of a sodium channel blocker, pilsicainide, during AF [1].
• RESULTS: Ventricular arrhythmia was not induced by administration of pilsicainide in 55 patients (no-VA group) [2].
• Administration of pilsicainide-induced VA in 10 patients (Pil-VA group) and polymorphic ventricular tachycardia in four patients [2].
• Ischemia enhances use-dependent sodium channel blockade by pilsicainide, a class IC antiarrhythmic agent [3].
• The aim of this study was to elucidate whether the electrophysiologic properties of pilsicainide, a novel class IC drug with slow kinetic properties, could be altered in the presence of acute myocardial ischemia [3].

High impact information on Pilsicainide

• In six cases, macroscopic TWA occurred in association with pilsicainide-induced VA, but TWA occurred in only one patient without pilsicainide-induced arrhythmia [2].
• Pilsicainide produced a rate-dependent prolongation of the QRS duration in patients without ST segment depression as the heart rate increased to 100 beats/min [3].
• A 72-year-old woman with renal insufficiency who was taking oral pilsicainide (150 mg/d) complained of feeling faint 3 days after she was prescribed oral cetirizine (20 mg/d) [4].
• Severe arrhythmia as a result of the interaction of cetirizine and pilsicainide in a patient with renal insufficiency: first case presentation showing competition for excretion via renal multidrug resistance protein 1 and organic cation transporter 2 [4].
• Coadministration of probenecid did not show any changes in plasma concentrations of pilsicainide, pharmacokinetics, or the net renal clearance by tubular secretion of pilsicainide [5].

Chemical compound and disease context of Pilsicainide

• Flecainide and pilsicainide, Class IC antiarrhythmic drugs with slow kinetics, were administered to a 64-year-old man experiencing ventricular tachycardia [6].
• To investigate effect of pilsicainide hydrochloride (pilsicainide) on electrocardiogram (ECG) signals and action potentials (APs) of atrial myocytes, levo-thyroxine (T4, 500 microg/kg body weight) was daily injected into peritoneal cavity of Sprague-Dawley rats for 14 days [7].
• The effects of pilsicainide on vagally induced atrial fibrillation and on electrophysiological parameters were compared with those of propafenone in alpha-chloralose-anesthetized dogs [8].
• Both pilsicainide and E-4031 preferentially blocked conduction in the specific area, leading to the termination of atrial flutter [9].
• Pilsicainide-induced verapamil sensitive idiopathic left ventricular tachycardia [10].

Biological context of Pilsicainide

• CONCLUSIONS: Pilsicainide appeared to be secreted by the active transport system for organic bases in the proximal tubule, and the excretion of pilsicainide was inhibited by cimetidine [5].
• Concentration-inhibition study demonstrated that pilsicainide significantly inhibited net inward current of T4-treated rats at lower concentration (IC50 of 29.2 microg/mL) than that of control rats (133 microg/mL) [7].
• These results suggest that pilsicainide, irrespective of intra- or extracellular application, shares a common binding site to block INa in cardiac myocytes [11].
• Pilsicainide increased the heart rate and mean pulmonary arterial pressure and decreased the stroke volume index at 60 min [12].
• Effect of protein binding of pilsicainide on the pharmacokinetics [13].

Anatomical context of Pilsicainide

• In patients with paroxysmal atrial fibrillation (AF), pilsicainide significantly prolonged the ERP of the distal pulmonary vein (PV), PV-left atrium (LA) junction and LA, and the conduction time from the distal PV to the PV-LA junction [14].
• Using an optical mapping system, we mapped APs on the epicardium or transmural surfaces of 28 isolated and arterially perfused canine right ventricular preparations having drug-induced Brugada syndrome (in micromol/l: 2.5-15 pinacidil, 5.0 terfenadine, and 5.0-13 pilsicainide) [15].
• Effect of sodium channel blocker, pilsicainide hydrochloride, on net inward current of atrial myocytes in thyroid hormone toxicosis rats [7].
• Sixty minutes after administration of a single oral dose of pilsicainide, the sinoatrial conduction time, AH and HV intervals, and the effective refractory period of the right ventricle were prolonged [12].
• Differentiation of the electrophysiological effects on the atrial myocardium between the pure na channel blocker, pilsicainide, and flecainide [16].

Associations of Pilsicainide with other chemical compounds

• Disopyramide, procainamide and pilsicainide produced negligible inhibition of phenacetin O-deethylation (IC50 >1 mM) [17].
• The effects of intavenous (1) pilsicainide 50 mg, (2) glucose 50 g, and (3) glucose 50 g plus regular insulin 10 IU on the precordial ECG leads were examined [18].
• The heart rate was decreased by pilsicainide and flecainide, but not by propafenone [19].
• By using representatives of 5 different categories of antiarrhythmic drugs, that is, pilsicainide, propranolol, nifekalant, verapamil, and amiodarone, we investigated whether these ion channel blockers or beta-antagonists affect cardiac apoptosis in cell cultures [20].

Gene context of Pilsicainide

• Pilsicainide significantly decreased AP amplitude (APA) and Max dV/dt in both control and T4-treated rat atrial cells [7].
• Conduction delay was increased (total QRS: 112.2 +/- 6.3 msec to 131.7 +/- 6.3 msec; under 40 microV: 42.0 +/- 8.5 msec to 52.7 +/- 12.7 msec; last 40 msec: 17.4 +/- 5.9 microV to 10.4 +/- 6.1 microV) on SAECG by pilsicainide [21].
• Effects of Na+ channel blocker, pilsicainide, on HERG current expressed in HEK-293 cells [22].
• These results suggest C/D is increased in patients with high CRP levels because of binding of pilsicainide to protein, resulting decreased clearance [13].
• Images in cardiology: Successful treatment of atrial tachycardia-induced cardiomyopathy with pilsicainide [23].

Analytical, diagnostic and therapeutic context of Pilsicainide

• In 25 patients with symptomatic attacks of paroxysmal atrial fibrillation, the signal-averaged ECG was repeated 1 h after a single dose of orally administered pilsicainide, a new class Ic drug [24].
• The concentration of pilsicainide in plasma and urine were determined by an HPLC method [5].
• Hybrid therapy with pilsicainide and PV isolation (by radiofrequency catheter ablation) appears to be an effective therapeutic approach for AF [14].
• Before oral administration of pilsicainide, 41 patients underwent transesophageal echocardiography to investigate whether there was thrombus formation in the heart chambers [25].
• RESULTS: Before cardioversion, 11 patients in the pilsicainide group (21%) reverted to sinus rhythm [25].

References