Document Detail


Electrophysiology of the enantiomers of disopyramide in dogs.
MedLine Citation:
PMID:  2413296     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The antiarrhythmic agent disopyramide comprises two enantiomers. In the present study, we examined the effects of the individual enantiomers on in vivo electrophysiology in anesthetized, closed-chest dogs. Six dogs received d-disopyramide, seven received l-disopyramide, and three dogs served as controls. Electrophysiologic measurements were performed at a series of geometrically increasing steady-state plasma concentrations of d- or l-disopyramide. Concentration-response curves were constructed for each electrophysiologic parameter, and the slopes of the regression lines of response versus plasma concentration were compared between enantiomers. Electrophysiologic parameters in the control dogs did not significantly change with time. However, stereoselective electrophysiologic effects were observed, with l-disopyramide being more potent than d-dispopyramide in prolonging sinus cycle length, Wenckebach cycle length, and atrioventricular nodal refractoriness (p less than 0.05). These findings are consistent with the established increased anticholinergic activity of the d-enantiomer which appeared to offset its local anesthetic or sodium channel inhibiting properties. Interrelationships between the autonomic nervous system and the cardiac electrophysiologic effects of disopyramide may be important in its antiarrhythmic effects.
Authors:
J C Giacomini; K M Giacomini; W L Nelson; D C Harrison; T F Blaschke
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  7     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:    1985 Sep-Oct
Date Detail:
Created Date:  1985-11-21     Completed Date:  1985-11-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  884-90     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Anesthesia
Animals
Atrioventricular Node / drug effects
Bundle of His / drug effects
Disopyramide / pharmacology*
Dogs
Electrocardiography*
Heart / drug effects*
Heart Conduction System / drug effects
Heart Rate / drug effects
Male
Stereoisomerism
Grant Support
ID/Acronym/Agency:
GM 22209/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
3737-09-5/Disopyramide

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


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