A placebo-controlled, randomized, double-blind, crossover study was performed in 14 patients with chronic, resistant, ventricular arrhythmias in order to evaluate the efficacy and safety of two new antiarrhythmic agents, propafenone and aprindine. After an initial placebo phase, patients received orally either propafenone (600 mg daily) or aprindine (150 mg daily for the first two days and 50 mg every 12 hours successively) for five days. This treatment was followed by a drug-free period (placebo II); patients were then crossed over to the alternative drug. A 24-hour Holter recording was performed during the last 48 hours of the initial placebo phase and on the final day of each phase of the crossover period. Analysis of Holter recordings revealed that the mean hourly PVCs frequency, for the group, was similar during the two control periods. Significant reduction in the mean hourly frequency of PVCs from control levels was observed in 78% of the patients during propafenone therapy and in 42% during aprindine therapy. For the whole group, propafenone induced a significant reduction of the average PVCs/h frequency (p less than 0.05), whereas the aprindine was ineffective. Finally no patient experienced side effects with propafenone, whereas aprindine caused side effects in three patients (dizziness, tremor, ataxy).
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Biol Pharm Bull
January 2023
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University.
The negative inotropic effects of nine Vaughan Williams class I antiarrhythmic drugs were examined in guinea pig ventricular tissue preparations. The drugs decreased the contractile force of papillary muscles with different potencies: the potency order was propafenone > aprindine > cibenzoline > flecainide > ranolazine > disopyramide > pilsicainide > mexiletine > GS-458967. The potency of drugs correlated with the reported IC values to block the L-type Ca channel rather than the Na channel.
View Article and Find Full Text PDFJ Pharmacol Sci
August 2020
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, 274-8510, Japan.
The effects of class I antiarrhythmic drugs on the automaticity of isolated guinea pig pulmonary vein myocardia were investigated using microelectrode and voltage clamp methods. All of the drugs examined reduced the maximum rate of rise of automatic action potentials. The firing frequency and rate of diastolic depolarization were decreased by aprindine, flecainide and propafenone, but not by cibenzoline, disopyramide and pilsicainide, which correlated with blockade of the sodium current component induced by ramp depolarization mimicking the diastolic depolarization.
View Article and Find Full Text PDFCochrane Database Syst Rev
August 2015
Iberoamerican Cochrane Network, Valencia, Venezuela.
Background: Coronary artery disease is a major public health problem affecting both developed and developing countries. Acute coronary syndromes include unstable angina and myocardial infarction with or without ST-segment elevation (electrocardiogram sector is higher than baseline). Ventricular arrhythmia after myocardial infarction is associated with high risk of mortality.
View Article and Find Full Text PDFJ Pharmacol Sci
June 2009
Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan.
After the report of the Cardiac Arrhythmia Suppression Trial, a tabular framework of the Sicilian Gambit has been proposed to display actions of antiarrhythmic drugs on ion channels and receptors and to provide more rational pharmacotherapy of arrhythmias. However, because effects of antiarrhythmic drugs on If have not been thoroughly examined, we used patch clamp techniques to determine the effects of various antiarrhythmic drugs on the HCN (hyperpolarization-activated cyclic nucleotide-gated) channel currents. HCN4 channels, a dominant isoform of HCN channels in the heart, were expressed in HEK293 cells.
View Article and Find Full Text PDFChirality
July 2009
Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
The interaction of propafenone (PPF) enantiomers with human plasma, human serum albumin (HSA), alpha(1)-acid glycoprotein (AGP), as well as with plasma from rat, rabbit, and cow was investigated using indirect chiral high performance liquid chromatography (HPLC) and ultrafiltration techniques. The stronger binding of the S-PPF found in human plasma was due to AGP. Two classes of binding sites in AGP were identified: one with high-affinity and small binding capacity (K(1(S)) = 7.
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