DOI: 10.1161/01.cir.91.6.1799. Ibutilide, a Methanesulfonanilide Antiarrhythmic, Is a Potent Blocker of the Rapidly Activating Delayed Rectifier K<sup>+</sup>Current (I<sub>Kr</sub>) in AT-1 Cells

Ibutilide, a Methanesulfonanilide Antiarrhythmic, Is a Potent Blocker of the Rapidly Activating Delayed Rectifier K+Current (IKr) in AT-1 Cells

10.1161/01.cir.91.6.1799

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation (276)

Abstract

BackgroundIbutilide is an action potential–prolonging antiarrhythmic currently in clinical trials. The drug shares structural similarities with E-4031 and dofetilide, specific blockers of the rapidly activating delayed rectifier K+current (IKr). However, previous in vitro studies in guinea pig myocytes have indicated that ibutilide does not block IKrbut rather increases a slow inward sodium current.Methods and ResultsIn this study, we compared the effects of ibutilide with those of dofetilide on outward current in mouse atrial tumor myocytes (AT-1 cells), a preparation in which, unlike guinea pig, a typical IKris the major delayed rectifier and can be readily recorded in isolation from other currents. In AT-1 cells, ibutilide and dofetilide were both potent IKrblockers, with EC50values of 20 (n=12) and 12 (n=8) nmol/L, respectively, at +20 mV. The time and voltage dependence of IKrinhibition by the two compounds were virtually identical. The following characteristics were most consistent with open channel block: (1) block increased with depolarizing pulses; (2) block increased with longer pulses; (3) currents deactivated more slowly in the presence of drug, resulting in a “crossover” typical of open channel block; and (4) with repetitive pulsing after drug wash-in, use-dependent block was observed.ConclusionsThese data suggest that the clinical actions of ibutilide are mediated at least in part by block of IKr; an effect on inward currents is not excluded. AT-1 cells are a useful model system for the study of drug block of this important repolarizing current.

Bibliography

Yang, T., Snyders, D. J., & Roden, D. M. (1995). Ibutilide, a Methanesulfonanilide Antiarrhythmic, Is a Potent Blocker of the Rapidly Activating Delayed Rectifier K+Current (IKr) in AT-1 Cells. Circulation, 91(6), 1799â1806.

Authors 3

Tao Yang (first)
Dirk J. Snyders (additional)
Dan M. Roden (additional)

References 35 Referenced 150

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10.1161/res.69.2.1860189

Dates

Type	When
Created	13 years, 2 months ago (June 11, 2012, 8:34 p.m.)
Deposited	5 months ago (March 30, 2025, 4:51 p.m.)
Indexed	1 month, 4 weeks ago (July 6, 2025, 1:45 p.m.)
Issued	30 years, 5 months ago (March 15, 1995)
Published	30 years, 5 months ago (March 15, 1995)
Published Print	30 years, 5 months ago (March 15, 1995)

Funders 0

None

BibTeX

@article{Yang_1995, title={Ibutilide, a Methanesulfonanilide Antiarrhythmic, Is a Potent Blocker of the Rapidly Activating Delayed Rectifier K+Current (IKr) in AT-1 Cells: Concentration-, Time-, Voltage-, and Use-Dependent Effects}, volume={91}, ISSN={1524-4539}, url={http://dx.doi.org/10.1161/01.cir.91.6.1799}, DOI={10.1161/01.cir.91.6.1799}, number={6}, journal={Circulation}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Yang, Tao and Snyders, Dirk J. and Roden, Dan M.}, year={1995}, month=mar, pages={1799–1806} }

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