Enantioselective Actions of Tocainide on the Electrophysiologic Properties of the Guinea Pig Papillary Muscle

Enantioselective Electrophysiologic Actions of Tocainide. The electrophysiologic effects of the R (−) and S(+) enantiomers of tocainide, a Class IB antiarrhythmic drug, were studied in the guinea pig papillary muscle, using the standard microelectrode technique. The results can be summarized as follows: (1) R(−) tocainide HCI, 100 mg/L (437 μM), was more potent in reducing the maximal rate of depolarization (τmax) than S(+) tocainide HCl. At a stimulation frequency of 1 Hz, in the presence of 5.4 mM external K+, τmax was reduced an average of 44% in the presence of R(−) tocainide while only 26% in the presence of S(+) tocainide. The inhibition was mainly due to tonic block. The amount of tonic block, as well as phasic block, were different for both enantiomers. (2) The recovery of drug‐occupied channels during the diastolic interval was slower in the presence of R(−) tocainide (τ= 491 msec) than in the presence of S(+) tocainide (τ= 241 msec). Decreasing the stimulation interval caused proportionally more reduction of Vmax in the presence of R(−) tocainide than in the presence of S(+) tocainide. (3) Voltage dependence of block of τmax was also more pronounced with R(−) tocainide. Inactivation curves were shifted toward more negative potentials of 14 mV in the presence of R(−) tocainide, while S(+) tocainide provoked a shift of only 7 mV.