Disease relevance of Cifenline

• This was a prospective single-blind, placebo-controlled study of cibenzoline in 21 patients with five or more runs of nonsustained ventricular tachycardia (VT) and left ventricular dysfunction (mean left ventricular ejection fraction 36 +/- 24%) [1].
• Antiarrhythmic efficacy and hemodynamic effects of cibenzoline in patients with nonsustained ventricular tachycardia and left ventricular dysfunction [1].
• Cibenzoline for treatment of ventricular arrhythmias: a double-blind placebo-controlled study [2].
• Cibenzoline plasma concentration was 59 to 421 ng/ml in responders and higher (387, 758 and 852 ng/ml, respectively) in the three subjects with side effects (right bundle branch block in one, hypotension in one, gastrointestinal upset and central nervous system complaints in one) [2].
• In these 18 patients, the mean atrial cycle length was prolonged from 147 +/- 34 ms during atrial fibrillation to 302 +/- 34 ms after cibenzoline (P < 0.001) [3].

Psychiatry related information on Cifenline

• Intravenous cibenzoline terminated AF in 8 patients (T group), but not in 7 patients (non-T group) [4].

High impact information on Cifenline

• Class Ia antiarrhythmic drug cibenzoline: a new approach to the medical treatment of hypertrophic obstructive cardiomyopathy [5].
• The aim of this study is to elucidate whether cibenzoline attenuates left ventricular pressure gradient (LVPG) in patients with HOCM [5].
• LVPG and left ventricular functions were measured before and 2 hours after administration of a single oral dose of 150 or 200 mg cibenzoline [5].
• Caution is recommended in the use of cibenzoline in patients with left ventricular ejection fractions of less than 25% [1].
• Cibenzoline did not affect electrophysiologic properties of the atrium or atrioventricular (AV) node [6].

Chemical compound and disease context of Cifenline

• In tachycardias involving accessory connections, agents that affect fast channel dependent tissue (propafenone, flecainide, cibenzoline, disopyramide or hydroquinidine) are effective [7].
• In a randomized, double-blind, parallel clinical trial, the authors tested and compared flecainide and cibenzoline, a new antiarrhythmic drug, on atrial arrhythmias [8].
• QT-prolonging class I drug, disopyramide, does not aggravate but suppresses adrenaline-induced arrhythmias. Comparison with cibenzoline and pilsicainide [9].
• Thus, cibenzoline was only slightly superior to quinidine in suppressing ventricular arrhythmias [10].
• We conclude that cibenzoline and glibenclamide, which block cardiac K(ATP) channels inhibit contractile recovery after reperfusion by attenuating the shortening of APD during ischemia [11].

Biological context of Cifenline

• However, in three of 21 patients (mean ejection fraction 21%), cibenzoline was discontinued due to severe depression of left ventricular function [1].
• Effect of renal impairment on the pharmacokinetics of cibenzoline [12].
• Oral cibenzoline kinetics were followed in 36 healthy subjects aged from 22 to 78 yr divided into groups of six subjects per decade between 20 and 80 yr [13].
• Single infusion of intravenous cibenzoline in the treatment of supraventricular tachyarrhythmias following heart surgery. A double-blind placebo-controlled parallel study [14].
• These results suggest that cibenzoline is effective for the treatment of postoperative supraventricular tachyarrhythmias in patients without impairment of ventricular function [14].

Anatomical context of Cifenline

• A markedly greater inhibition by cibenzoline (20 microM) was recorded when myocytes were depolarized (to +20 mV) from a holding potential of -35 mV than of -80 mV [15].
• The authors conclude that cibenzoline acts as a class la antiarrhythmic agent in guinea pig papillary muscle [16].
• Electrophysiological study of cibenzoline in voltage-clamped rabbit sinoatrial node preparations [17].
• Inhibition of the ATP-sensitive potassium channel by class I antiarrhythmic agent, cibenzoline, in rat pancreatic beta-cells [18].
• 5. The binding of [3H]-glibenclamide to pancreatic islets was inhibited by glibenclamide but not by cibenzoline [19].

Associations of Cifenline with other chemical compounds

• The effect of class I anti-arrhythmic drugs, cibenzoline, mexiletine and flecainide, on the delayed rectifier potassium current (IK) in guinea-pig ventricular myocytes was studied using whole cell voltage clamp techniques and under blockade of the L-type calcium current by 5 microM nitrendipine [20].
• Modulation by class Ia antiarrhythmic drugs, cibenzoline and disopyramide, of the pacemaking activity and the underlying ionic currents in rat sino-atrial nodal cells was investigated using current-clamp and whole-cell patch-clamp techniques [21].
• Employing an incremental dose titration protocol, cibenzoline (130 mg twice daily and 160 mg twice daily) and quinidine (300 mg every 6 hours and 400 mg every 6 hours) were administered for 7 days at each dose level, with preceding washout periods [22].
• Stereoselective metabolism of cibenzoline succinate, an oral antiarrhythmic drug, was investigated on hepatic microsomes from humans and rats and microsomes from cells expressing human cytochrome P450s (CYPs) [23].
• In the isolated pancreas perfused in the presence of a slightly stimulating glucose concentration (8.3 mM), cibenzoline (2 and 6 microM) elicited a progressive and sustained insulin response in a concentration-dependent manner [24].

Gene context of Cifenline

• These results provide evidence that CYP3A and CYP2D play a major role in the stereoselective metabolism of cibenzoline in humans and male rats [23].
• Stereoselective metabolism of cibenzoline, an antiarrhythmic drug, by human and rat liver microsomes: possible involvement of CYP2D and CYP3A [23].
• In contrast, cibenzoline inhibited equally Kir6.2DeltaC26 and Kir6.2DeltaC26 + SUR1 channels, in a dose-dependent manner, the half-maximal concentrations of channel inhibition being 22.2 +/- 6.1 and 30.9 +/- 9.4 microM, respectively [25].
• The antiarrhythmic agent cibenzoline inhibits KATP channels by binding to Kir6.2 [25].
• A similar IC50 value of 2.5 microM (h = 1.2 at -60 mV under symmetrical approximately 150 mM K+) was observed for cibenzoline induced block of KATP channels [26].

Analytical, diagnostic and therapeutic context of Cifenline

• Hemodynamic measurements were obtained with the use of right heart catheterization in patients at rest and exercising during the placebo phase and after 60 hr of oral cibenzoline [1].
• Cibenzoline plasma and urine concentrations were measured by HPLC [13].
• Left ventricular function by radionuclide ventriculography and plasma cibenzoline levels were measured at frequent intervals [27].
• This observation suggests that cibenzoline, like other antiarrhythmic agents, can be responsible for neuromuscular blockade, and should therefore be used with caution in patients with neuromuscular and respiratory diseases or with impaired renal function [28].
• Muscle strength recovered as serum cibenzoline levels decreased, allowing the patient to be weaned from the ventilator [28].

References