title: Different electrophysiological effects of the levo- and dextro-rotatory isomers of mexiletine in isolated rabbit cardiac muscle.
abstract: 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/APD90ratio. 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.
authors.affiliation: a Department of Pharmacology & Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Gurabi
authors.affiliation: a Department of Pharmacology & Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.|b First Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.|c DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg-Mannheim, Germany.
authors.forename: Bence
authors.initials: B
authors.lastname: Patocskai
authors.affiliation: d Faculty of Dentistry, University of Szeged, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Györe
authors.affiliation: a Department of Pharmacology & Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Virág
authors.affiliation: e Department of Organic Chemistry, Faculty of Pharmacology, Semmelweis University, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Mátyus
authors.affiliation: a Department of Pharmacology & Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.|f Hungarian Academy of Sciences - University of Szeged (MTA-SZTE) Research Group of Cardiovascular Pharmacology, Szeged, Hungary.
authors.forename: Julius Gy
authors.initials: JG
authors.lastname: Papp
authors.affiliation: a Department of Pharmacology & Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.|f Hungarian Academy of Sciences - University of Szeged (MTA-SZTE) Research Group of Cardiovascular Pharmacology, Szeged, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Varró
authors.affiliation: a Department of Pharmacology & Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Koncz
mesh_terms: D000818:Animals; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008801:Mexiletine / Q000737:chemistry* / Q000494:pharmacology*; D011817:Rabbits; D012399:Rotation; D013237:Stereoisomerism
chemical_list: D008801:Mexiletine
keywords: D-(−) mexilétine, L-(+) mexilétine, muscles papillaires,; R-(−) mexiletine, S-(+) mexiletine, papillary muscles,; conduction time; early extrasystoles; extrasystoles précoces; temps de conduction