Different electrophysiological effects of the levo- and dextro-rotatory isomers of mexiletine in isolated rabbit cardiac muscle

作者：Gurabi Zsolt; Patocskai Bence; Gyore Balazs; Virag Laszlo; Matyus Peter; Papp Julius Gy; Varro Andras^*; Koncz Istvan

来源：Canadian Journal of Physiology and Pharmacology, 2017, 95(7): 830-836.

DOI：10.1139/cjpp-2016-0599

• R-(-) mexiletine
• S-(+) mexiletine
• papillary muscles
• V-max
• conduction time
• early extrasystoles

Racemic mexiletine is a widely used antiarrhythmic agent that blocks sodium channels. The effects of R-(-) and S-(+) mexiletine stereoisomers on maximum rate of depolarization (V-max), conduction time, and repolarization have not yet been investigated in isolated cardiac preparations. We studied the effect of the R-(-) and S-(+) mexiletine on rabbit cardiac action potential parameters by using the conventional microelectrode technique. Both enantiomers at 20 mu mol/L of therapeutically and experimentally relevant concentration, significantly depressed the V-max at fast heart rates (BCLs 300-700 ms). R-(-) mexiletine has more potent inhibitory effect than S-(+) mexiletine. Both R-(-) and S-(+) mexiletine significantly inhibited the V-max of early extrasystoles measured at 70 ms diastolic interval induced by S1-S2 stimuli. R-(-) mexiletine has more pronounced inhibitory effect than S-(+) mexiletine. Both R-(-) and S-(+) mexiletine increased significantly the ERP/APD90 ratio. The time constant (tau)of recovery of V-max was found to be tau = 376.0 +/- 77.8 ms for R-(-) mexiletine and tau = 227.1 +/- 23.4 ms for S-(+) mexiletine, which indicates a slower offset kinetics for R-(-) mexiletine from sodium channels than that of the S-(+) enantiomer. These data suggest that R-(-) mexiletine might be a more potent antiarrhythmic agent than S-(+) mexiletine.

• 出版日期2017-7