The cellular electrophysiologic effect of a new amiodarone like antiarrhythmic drug GYKI 16638 in undiseased human ventricular muscle: Comparison with sotalol and mexiletine

M. Opincariu, A. Varró, N. Jost, L. Virág, O. Hála, J. Szolnoki, J. Szécsi, G. Bogáts, P. Szenohradszky, P. Mátyus, J. Papp

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Abstract

The cellular electrophysiologic effect of GYKI 16638, a new antiarrhythmic compound was studied and compared with that of sotalol and mexiletine in undiseased human right ventricular muscle preparation by applying the conventional microelectrode technique. GYKI 16638 (5 μM), at stimulation cycle length of 1000 ms, lengthened action potential duration (APD90) from 338.9 ± 28.6 ms to 385.4 ± 24 ms (n = 9, p <0.05). This APD lengthening effect, unlike that of sotalol (30 μM), was rate-independent. GYKI 16638, contrary to sotalol and like mexiletine (10 μM), exerted a use-dependent depression of the maximal rate of depolarization (Vmax) which amounted to 36.4 ± 11.7% at cycle length of 400 ms (n = 5, p <0.05) and was characterised with an offset kinetical time constant of 298.6 ± 70.2 ms. It was concluded that GYKI 16638 in human ventricular muscle shows combined Class IB and Class III antiarrhythmic properties, resembling the electrophysiological manifestation seen after chronic amiodarone treatment.

Original languageEnglish
Pages (from-to)41-46
Number of pages6
JournalCurrent Medicinal Chemistry
Volume9
Issue number1
Publication statusPublished - 2002

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Mexiletine
Sotalol
Amiodarone
Anti-Arrhythmia Agents
Muscle
Muscles
pamidronate
Microelectrodes
Depolarization
Action Potentials
GYKI 16638

ASJC Scopus subject areas

  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology

Cite this

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title = "The cellular electrophysiologic effect of a new amiodarone like antiarrhythmic drug GYKI 16638 in undiseased human ventricular muscle: Comparison with sotalol and mexiletine",
abstract = "The cellular electrophysiologic effect of GYKI 16638, a new antiarrhythmic compound was studied and compared with that of sotalol and mexiletine in undiseased human right ventricular muscle preparation by applying the conventional microelectrode technique. GYKI 16638 (5 μM), at stimulation cycle length of 1000 ms, lengthened action potential duration (APD90) from 338.9 ± 28.6 ms to 385.4 ± 24 ms (n = 9, p <0.05). This APD lengthening effect, unlike that of sotalol (30 μM), was rate-independent. GYKI 16638, contrary to sotalol and like mexiletine (10 μM), exerted a use-dependent depression of the maximal rate of depolarization (Vmax) which amounted to 36.4 ± 11.7{\%} at cycle length of 400 ms (n = 5, p <0.05) and was characterised with an offset kinetical time constant of 298.6 ± 70.2 ms. It was concluded that GYKI 16638 in human ventricular muscle shows combined Class IB and Class III antiarrhythmic properties, resembling the electrophysiological manifestation seen after chronic amiodarone treatment.",
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T2 - Comparison with sotalol and mexiletine

AU - Opincariu, M.

AU - Varró, A.

AU - Jost, N.

AU - Virág, L.

AU - Hála, O.

AU - Szolnoki, J.

AU - Szécsi, J.

AU - Bogáts, G.

AU - Szenohradszky, P.

AU - Mátyus, P.

AU - Papp, J.

PY - 2002

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