Details

Autor(en) / Beteiligte

• Gurabi, Zsolt
• Patocskai, Bence
• Györe, Balázs
• Virág, László
• Mátyus, Péter
• Papp, Julius Gy
• Varró, András
• Koncz, István

Titel

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

Ist Teil von

• Canadian journal of physiology and pharmacology, 2017-07, Vol.95 (7), p.830

Ort / Verlag

Canada

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 ([Formula: see text]), 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 μmol/L of therapeutically and experimentally relevant concentration, significantly depressed the [Formula: see text] 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 [Formula: see text] 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/APD ratio. The time constant (τ) of recovery of [Formula: see text] was found to be τ = 376.0 ± 77.8 ms for R-(-) mexiletine and τ = 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.