Document Detail


Antiarrhythmic effects of optical isomers of disopyramide on canine ventricular arrhythmias.
MedLine Citation:
PMID:  8907798     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Disopyramide is an effective class I antiarrhythmic drug and widely used for the treatment of arrhythmias, but it has anticholinergic side effects. In vitro studies demonstrated that dextrorotatory (D-) disopyramide has a stronger anticholinergic action, whereas the levorotatory (L-) isomer has a stronger Na channel blocking action. Because the antiarrhythmic mechanism of disopyramide suppressing digitalis- and two-stage coronary ligation-induced canine ventricular arrhythmias is the drug-induced Na channel block, we examined the antiarrhythmic efficacy of D- and L-disopyramide on two arrhythmia models. On ouabain-induced ventricular tachycardia (VT), L-disopyramide 3 mg/kg decreased the arrhythmic ratio (number of ectopic beats/total heart rate), whereas the same dose of the D-isomer was ineffective and a higher dose (5 mg/kg) was needed to suppress the arrhythmia. The effective plasma concentrations (IC50) decreasing the arrhythmic ratio to 50% of the control were 5.3 and 11.3 mu g/ml for L- and D-disopyramide, respectively. We obtained similar results using 24-h two-stage coronary ligation VT. The IC50 were 8.9 and 22.2 mu g/ml for the L- and D-isomers, respectively. Our results indicate that L-disopyramide is about twice as strong an antiarrhythmic drug as the D-isomer.
Authors:
M Nakamura; Y Xue; K Eto; K Hashimoto
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  27     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1996 Mar 
Date Detail:
Created Date:  1997-03-13     Completed Date:  1997-03-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  368-75     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Yamanashi Medical University, Japan.
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MeSH Terms
Descriptor/Qualifier:
Action Potentials / drug effects
Animals
Anti-Arrhythmia Agents / pharmacology*
Arrhythmias, Cardiac / drug therapy*
Coronary Disease / complications
Digitalis
Disopyramide / pharmacology*,  therapeutic use
Dogs
Electrocardiography
Female
Male
Plants, Medicinal
Plants, Toxic
Stereoisomerism
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 3737-09-5/Disopyramide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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