Kinetics of onset of rate-dependent effects of Class I antiarrhythmic drugs are important in determining their effects on refractoriness in guinea-pig ventricle, and provide a theoretical basis for their subclassification

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Abstract
The kinetics of onset of rate-dependent depression of maximum rate of depolarisation (V̇(max) of guinea-pig ventricular action potentials were studied for nine Class I anti-arrhythmic drugs using standard microelectrode techniques. The drugs were found to fall into three well-demarcated subgroups with “fast” (lignocaine, tocainide and mexiletine), “intermediate” (quinidine, disopyramide and procainamide) and “slow” (flecainide, encainide and lorcainide) kinetics. The “fast” drugs were found to share the ability to markedly prolong the effective refractory period (ERP) relative to the action potential duration (APD). The “slow” drugs had only minor effects on this parameter. The “intermediate” drugs produced small to moderate increases in ERP relative to APD but in addition significantly prolonged APD, which was shortened by the “fast” drugs. Thus, using the parameters of speed of onset of rate-dependent depression of V̇max and APD it was possible to subdivide the nine Class I drugs into three distinct subclasses.