Different electrophysiological effects of the levo- and dextro-rotatory isomers of mexiletine in isolated rabbit cardiac muscle
Racemic mexiletine is a widely used antiarrhythmic agent which blocks sodium channels. The effects of R-(-) and S-(+) mexiletine stereoisomers on maximum rate of depolarization (Vmax), conduction time and repolarization have not yet been investigated in isolated cardiac preparations. We studied the...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2017
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| Sorozat: | CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
95 No. 7 |
| doi: | 10.1139/cjpp-2016-0599 |
| mtmt: | 3190137 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/15881 |
| Tartalmi kivonat: | Racemic mexiletine is a widely used antiarrhythmic agent which blocks sodium channels. The effects of R-(-) and S-(+) mexiletine stereoisomers on maximum rate of depolarization (Vmax), 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 microM of therapeutically and experimentally relevant concentration, significantly depressed the Vmax 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 Vmax 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 Vmax 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 more potent antiarrhythmic agent than S-(+) mexiletine. |
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| Terjedelem/Fizikai jellemzők: | 830-836 |
| ISSN: | 0008-4212 |