Electrophysiological effects of the optical isomers of disopyramide and quinidine in the dog. Dependence on stereochemistry.

Abstract

SUMMARY We studied the electrophysiological effects of the optical isomers of disopyramide and quinidine on canine cardiac Purkinje fibers. Conventional microelectrode techniques were employed to study the effects of racemic disopyramide, (+)-disopyramide, (-)-disopyramide, quinidine, and quinine. Racemic disopyramide, (+)-disopyramide, and quinidine prolonged action potential duration (APD) measured at 90% repolarization. In contrast, (-)-disopyramide and quinine shortened APD. These directionally opposite effects on repolarization were observed throughout 60 minutes exposure to drug and were concentration-dependent. All five compounds reduced dV/dt of phase 0, increased conduction time, and increased the current requirement for all-or-none depolarization. The effects of all five compounds on dV/dt, conduction time, and current requirements were time-and concentration-dependent. Our results indicate that the stereochemical configurations of disopyramide and quinidine determine their effects on repolarization of cardiac Purkinje fibers. Circ Res 48: 867-874, 1981

Mechanisms of action of lidocaine and quinidine on action potential duration in rabbit cardiac Purkinje fibers. An effect on steady state sodium currents?

“…potential. At therapeutic concentrations (2-5 \i%/ ml), lidocaine shortens action potential duration (Bigger and Mandel, 1970), whereas quinidine usually produces a lengthening at fixed cycle length (e.g., Mirro et al, 1981). Qualitatively similar effects occur in rabbit cardiac Purkinje fibers, as illustrated in Figure 1.…”

“…Additional effects on the cardiac membrane have also been indicated. At clinically relevant concentrations (2-5 jig/ml), lidocaine is known to shorten the cardiac action potential (Davis and Temte, 1969;Bigger and Mandel, 1970), whereas quinidine generally produces a lengthening September 17, 1981. or no change (Vaughan Williams, 1958;Hoffman, 1958;Mirro et al, 1981). The basis for the quinidine effect on action potential duration has not been defined, whereas an increase of potassium conductance has been proposed to mediate the action of lidocaine (Arnsdorf and Bigger, 1972;Weld and Bigger, 1976).…”

A receptor for type I antiarrhythmic drugs associated with rat cardiac sodium channels.

“…17 When tested in the radioligand binding assay, the D and L optical isomers had IC,,, values of 122 ±45 and 109 ± 6 /JLM, respectively. Thus, the stereoisomers of tocainide had stereospecific effects on both prolonging conduction time and …”

Differing electrophysiological effects of class IA, IB and IC antiarrhythmic drugs on guinea‐pig sinoatrial node

“…Such depression is seen somewhat more often with IA drugs (Birkhead & Vaughan Williams, 1977;Dhingra & Rosen, 1979). Furthermore the anticholinergic properties of quinidine and disopyramide (Mirro et al, 1981) undoubtedly contribute to the low incidence of clinical sinus node dysfunction seen with these drugs. This has been confirmed by recent studies on cardiac transplant patients, whose denervated hearts routinely respond to these drugs with significant increases in spontaneous cycle length (Mason et al, 1977;Bexton et al, 1984).…”