Comparison of Anticholinergic Effects of Cibenzoline, Disopyramide, and Atropine

Cazes, Matthias de; Chassaing, Chantal; Martinet, M; Cloarec, A.; Provost, Daniel; Boucher, Michel; Duchêne-Marullaz, P

doi:10.1097/00005344-199002000-00019

Cited by 21 publications

(18 citation statements)

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“…[23][24][25] In the present study, we confirmed that intravenous administration of cibenzoline can attenuate LV diastolic pressures, LV diastolic dysfunction and the LVPG. In contrast to disopyramide, the anticholinergic actions of cibenzoline are very weak, 26 so it may become an important therapeutic strategy in the management of patients not only with HOCM, but also those with HNCM.…”

Section: Discussionmentioning

confidence: 99%

Effect of Intravenous Administration of Cibenzoline on Left Ventricular Diastolic Pressures in Patients With Hypertrophic Cardiomyopathy Its Relationship to Transmitral Doppler Flow Profiles

Hamada

Aono

Ikeda

et al. 2007

Circ J

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he left ventricular pressure gradient (LVPG) is related to prognosis in patients with hypertrophic cardiomyopathy (HCM). 1,2 Ventriculomyectomy, DDD pacing and percutaneous transluminal septal myocardial ablation decrease the LVPG, and medical therapy is also known to decrease it. Of the drugs used, the class Ia antiarrhythmic drug disopyramide has been successfully used for the first time. 3,4 Pollick et al 5 and Kimball et al 6 also examined the acute hemodynamic effects of intravenous disopyramide in patients with hypertrophic obstructive cardiomyopathy (HOCM), and reported that the LVPG and the left ventricular end-diastolic pressure (LVEDP) were significantly decreased. The suggested mechanism was the negative inotropic action of disopyramide and an indirect effect associated with reduction of the LVPG and mitral regurgitation. 5 Another class Ia antiarrhythmic drug, cibenzoline, has attenuated the LVPG in patients with HOCM,7,8 as well as improving left ventricular (LV) diastolic dysfunction in both patients with HOCM 7 and hypertrophic nonobstructive cardiomyopathy (HNCM). 9 We interpret that this beneficial effect of cibenzoline might be caused by a decrease in both the left atrial and LV diastolic pressures, 7,9,10 but there are contradictory opinions about this. 11 In this study, to elucidate the effect of cibenzoline on LV hemodynamics in patients with HCM, aortic and LV pressures and LV diastolic function were examined before and after the intravenous administration of cibenzoline in patients with HOCM and HNCM. Methods Study SubjectsSixteen patients with HCM participated in this study after giving written informed consent and the protocol was approved by the Human Investigations Committee of Uwajima City Hospital and Ehime University School of Medicine. Diagnosis of HCM was made according to the World Health Organization/International Society and Federation of Cardiology definition of cardiomyopathies. 12 Of the 16 patients with HCM, 7 had HOCM and 9 had HNCM. Diagnosis of HOCM was made when the LVPG was more than 30 mmHg without provocation. Study ProtocolNo other drugs were administered after the admission. Cardiac catheterization was performed on day 3 of admission. After confirmation of normal coronary arteriograms, the following studies were performed. To monitor the LV and aortic pressures, 1 catheter was placed in the left ventricle and the other in the ascending aorta, and then 1.4 mg/kg Effect of Intravenous Administration of Cibenzoline on Left Ventricular Diastolic Pressures in Patients With Hypertrophic Cardiomyopathy Its Relationship to Transmitral Doppler Flow ProfilesMareomi Hamada, MD; Jun Aono, MD; Shuntaro Ikeda, MD; Kouki Watanabe, MD; Shinji Inaba, MD*; Jun Suzuki, MD*; Tomoaki Ohtsuka, MD*; Yuji Shigematsu, MD* Background Cibenzoline is able to improve left ventricular (LV) diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM), but the exact mechanism remains to be determined. Methods and ResultsThe present study was designed to elucidate the effect of intrav...

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Section: Discussionmentioning

confidence: 99%

Effect of Intravenous Administration of Cibenzoline on Left Ventricular Diastolic Pressures in Patients With Hypertrophic Cardiomyopathy Its Relationship to Transmitral Doppler Flow Profiles

Hamada

Aono

Ikeda

et al. 2007

Circ J

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“…62 In isolated guinea pig ileum, disopyramide was about 15 times more strongly anticholinergic than cibenzoline. 62 According to antagonism of the negative chronotropic effect of vagal stimulation in anesthetized dogs, intravenously administered cibenzoline was shown to be several times less potent than disopyramide. 62 Cibenzoline may not affect cardiac sympathetic -receptors, because it does not inhibit the positive chronotropic effect of isoproterenol on isolated rabbit SA node tissue preparations or dog Purkinje fibers.…”

Section: Receptors and Pumpsmentioning

confidence: 99%

“…Cazes et al compared the anticholinergic effects of cibenzoline with those of disopyramide in vitro and in vivo animal experiments. 62 Respective Ki values for inhibition of specific binding of 3 H-quinuclidinyl benzylate ( 3 H-QNB) of cibenzoline and disopyramide were 15.8 mol/L and 12.0 mol/L in a rat heart membrane preparation, and 31.6 mol/L and 7.8 mol/L in cerebral cortical membranes. 62 In isolated guinea pig ileum, disopyramide was about 15 times more strongly anticholinergic than cibenzoline.…”

Section: Receptors and Pumpsmentioning

confidence: 99%

“…62 Respective Ki values for inhibition of specific binding of 3 H-quinuclidinyl benzylate ( 3 H-QNB) of cibenzoline and disopyramide were 15.8 mol/L and 12.0 mol/L in a rat heart membrane preparation, and 31.6 mol/L and 7.8 mol/L in cerebral cortical membranes. 62 In isolated guinea pig ileum, disopyramide was about 15 times more strongly anticholinergic than cibenzoline. 62 According to antagonism of the negative chronotropic effect of vagal stimulation in anesthetized dogs, intravenously administered cibenzoline was shown to be several times less potent than disopyramide.…”

Section: Receptors and Pumpsmentioning

confidence: 99%

“…62 According to antagonism of the negative chronotropic effect of vagal stimulation in anesthetized dogs, intravenously administered cibenzoline was shown to be several times less potent than disopyramide. 62 Cibenzoline may not affect cardiac sympathetic -receptors, because it does not inhibit the positive chronotropic effect of isoproterenol on isolated rabbit SA node tissue preparations or dog Purkinje fibers. 47,49 No reports to date have shown significant effects of cibenzoline on -adrenergic receptors, A1 receptors, or sarcolemmal Na/K pumps in the heart.…”

Section: Receptors and Pumpsmentioning

confidence: 99%

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Profiles of Aprindine, Cibenzoline, Pilsicainide and Pirmenol in the Framework of the Sicilian Gambit

et al. 1999

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Canine plasma concentration‐cardiovascular effect relationships for bidisomide, a new antiarrhythmic drug, and disopyramide, cibenzoline, and propafenone

Garthwaite¹,

Schmidt²,

Hatley³

et al. 1995

Drug Development Research

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Bidisomide (SC-40230) is a unique new antiarrhythmic agent. In this study the canine intravenous (I.v.) antiarrhythmic doses of bidisomide (9 & 1 mg/kg), disopyramide (8 * 1 mgikg), cibenzoline (8 -+ 2 mg/kg), and propafenone (6 k 0.5 mg/kg) were established in a 24 h coronary ligation ventricular arrhythmia model. Based on the canine therapeutic doses of the four agents, three cumulative i.v. doses (load/maintenance infusions) of each of these drugs and placebo were then studied in normal anesthetized dogs to evaluate their general cardiovascular effects. Propafenone (0.7-3.0 @ml plasma concentration) caused potent reductions in cardiac output and increases in QRS duration relative to the other agents. Cibenzoline (0.S7.0 pgiml) and disopyramide (1.4-12.9 pgiml), at matched plasma concentrations, caused very similar cardiac output reductions, but cibenzoline caused nearly double the QRS increase. Bidisomide (1.9-16.1 pg/ml) had the least potent effects on cardiac output and QRS duration. All four drugs increased PR and QT in addition to QRS, but only disopyramide and propafenone increased JT (QT-QRS). These experiments suggest that the antiarrhythmic plasma concentrations of bidisornide, in contrast t o those of selected reference agents, do not cause prominent ventricular conduction slowing or prolongation of ventricular repolarization, and in addition, cause only modest hemodynamic effects in normal dogs. @ 1995 ~i l e y -~i s s , Inc

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Comparison of Anticholinergic Effects of Cibenzoline, Disopyramide, and Atropine

Cited by 21 publications

References 0 publications

Effect of Intravenous Administration of Cibenzoline on Left Ventricular Diastolic Pressures in Patients With Hypertrophic Cardiomyopathy Its Relationship to Transmitral Doppler Flow Profiles

Effect of Intravenous Administration of Cibenzoline on Left Ventricular Diastolic Pressures in Patients With Hypertrophic Cardiomyopathy Its Relationship to Transmitral Doppler Flow Profiles

Profiles of Aprindine, Cibenzoline, Pilsicainide and Pirmenol in the Framework of the Sicilian Gambit

Canine plasma concentration‐cardiovascular effect relationships for bidisomide, a new antiarrhythmic drug, and disopyramide, cibenzoline, and propafenone

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