Electrophysiology of the enantiomers of disopyramide in dogs.
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.
Giacomini
J C
JC
Giacomini
K M
KM
Nelson
W L
WL
Harrison
D C
DC
Blaschke
T F
TF
D000758:Anesthesia; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects; D002036:Bundle of His / Q000187:drug effects; D004206:Disopyramide / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D013237:Stereoisomerism
D004206:Disopyramide