| Antiarrhythmic effects of optical isomers of disopyramide on canine ventricular arrhythmias. | |
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MedLine Citation:
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PMID: 8907798 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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M Nakamura; Y Xue; K Eto; K Hashimoto |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 27 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 1996 Mar |
Date Detail:
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Created Date: 1997-03-13 Completed Date: 1997-03-13 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 368-75 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Yamanashi Medical University, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Action Potentials
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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:
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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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