| Description: |
Quinidine sulfate has antiarrhythmic efficacy. Quinidine is a non-specific ionic channel blocker that inhibits all the membrane currents in the atrioventricular node including the acetylcholine-activated K+ current. |
| Targets: |
Potassium Channel |
| In vitro: |
| Archiv Für Experimentelle Pathologie Und Pharmakologie, 1990, 341(6):517-524. | | Anticholinergic action of quinidine sulfate in the rabbit atrioventricular node.[Reference: WebLink] |
METHODS AND RESULTS:
Anticholinergic action of quinidine sulfate was electrophysiologically studied by recording spontaneous action potentials and membrane current of the rabbit atrioventricular node. In the presence of 0.1 mumol/l carbachol, the spontaneous activity of the atrioventricular nodal preparations was markedly inhibited, whereas subsequent addition of 1, 5 and 20 mumol/l quinidine restored automaticity in a concentration-dependent manner. In some preparations, quinidine at concentrations of 5 mumol/l and higher slowed the spontaneous activity by its direct membrane action even in the presence of carbachol. The dose-response curve for acetylcholine action on the spontaneous firing frequency showed that one molecule of acetylcholine bound to one muscarinic receptor of the atrioventricular node cell (Hill coefficient = 1.2). A parallel shift of this curve towards higher acetylcholine concentrations was observed at 0.03, 0.1 and 0.3 mumol/l but not at 1 and 3 mumol/l quinidine, suggesting a noncompetitive antagonism of quinidine against acetylcholine. Voltage clamp experiments revealed that 5 mumol/l quinidine reduced the slow inward current, hyperpolarization-activated inward current, and delayed rectifying K+ current, through its membrane actions. Quinidine at this concentration almost completely suppressed the acetylcholine-activated K+ current, which showed a relaxation phenomenon. Hence, the direct blockage of the acetylcholine-activated K+ current by quinidine was considered responsible for the anticholinergic action of this drug.
CONCLUSIONS:
We conclude that quinidine is a non-specific ionic channel blocker that inhibits all the membrane currents in the atrioventricular node including the acetylcholine-activated K+ current. |
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| In vivo: |
| American journal of cardiology, 1985, 56(10):581-585. | | Comparative efficacy and safety of oral tocainide and quinidine for benign and potentially lethal ventricular arrhythmias.[Reference: WebLink] |
METHODS AND RESULTS:
The antiarrhythmic efficacy and safety of oral tocainide hydrochloride and quinidine sulfate were compared in a double-blind, 3-center, parallel trial involving 133 patients with benign and potentially lethal ventricular arrhythmias. Baseline demographic, etiologic, functional and ventricular arrhythmia data were not significantly different between the 2 groups. Two weeks of an initial placebo period were followed by 8 weeks of active drug treatment, concluding with 4 weeks of washout. Frequent 24-hour ambulatory electrocardiographic monitoring was used to judge efficacy. Ten of 27 patients (37%) receiving tocainide and 12 of 24 patients (50%) receiving quinidine had a 75% reduction with drug treatment compared with the initial placebo period (p >0.25). Total abolition of ventricular tachycardia occurred in 6 of 16 patients (37%) receiving tocainide and 6 of 13 patients (43%) receiving quinidine (p >0.25). Conditions that required discontinuation of therapy occurred in 18 of 67 patients (27%) receiving tocainide and 16 of 66 (24%) receiving quinidine (difference not significant). More patients had dizziness during tocainide treatment and diarrhea during quinidine treatment. Quinidine caused a prolongation in the QT interval (0.03 second); tocainide caused a slight reduction (0.01 second). No important changes in vital signs or laboratory measurements were observed in left ventricular ejection fraction when measured.
CONCLUSIONS:
Thus, tocainide, the new oral analog of lidocaine, appears to be as safe as quinidine but is slightly less effective in suppressing ventricular arrhythmias. |
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