The Cellular Electrophysiologic Effect of A New Amiodarone Like Antiarrhythmic Drug GYKI 16638 in Undiseased Human Ventricular Muscle: Comparison With Sotalol And Mexiletine

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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 M), 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 M), was rate-independent. GYKI 16638, contrary to sotalol and like mexiletine (10 M), exerted a use-dependent depression of the maximal rate of depolarization (Vmax) which amounted to 36.4 ± 11.7 percent at cycle length of 400 ms (n = 5, p 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.

Keywords: Antiarrhythmic; Mexiletine; Sotalol

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867023371517

Publication date: January 1, 2002

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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