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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Inhibitory effect of the class III antiarrhythmic drug nifekalant on HERG channels: mode of action.

Nifekalant is a class III antiarrhythmic drug that has been shown to be effective against ventricular tachyarrhythmias in experimental animals and humans. We examined the detailed electrophysiological effects of nifekalant on human-ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes. Nifekalant inhibited the HERG current in a concentration-dependent manner with an IC(50) value of 7.9 microM although the drug did not inhibit the minK current in Xenopus oocytes, suggesting selective inhibition of the rapid component of the delayed rectifier K(+) current (I(Kr)) in cardiomyocytes. Nifekalant showed a higher binding affinity for the open state than for the inactive state of HERG channels. Nifekalant inhibited HERG channels in a frequency-dependent manner. The onset of the blockade was rapid but the recovery from the block was slow. Nifekalant modified the voltage dependence and kinetics of HERG channel gating. Thus, nifekalant inhibits HERG channels in a voltage-dependent and frequency-dependent manner, and the inhibitory effect may underlie the clinical efficacy of the drug against ventricular tachyarrhythmias.[1]


  1. Inhibitory effect of the class III antiarrhythmic drug nifekalant on HERG channels: mode of action. Kushida, S., Ogura, T., Komuro, I., Nakaya, H. Eur. J. Pharmacol. (2002) [Pubmed]
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