Block of HERG Potassium Channels by the Antihistamine Astemizole and its Metabolites Desmethylastemizole and Norastemizole

@article{Zhou1999BlockOH,
  title={Block of HERG Potassium Channels by the Antihistamine Astemizole and its Metabolites Desmethylastemizole and Norastemizole},
  author={Z Zhou and Vicken R. Vorperian and Qiuming Gong and S Zhang and Craig T. January},
  journal={Journal of Cardiovascular Electrophysiology},
  year={1999},
  volume={10}
}
Electrophysiologic Effects of Astemizole Metabolites. Introduction: The selective H1‐receptor antagonist astemizole (Hismanal) causes acquired long QT syndrome. Astemizole blocks the rapidly activating delayed rectifier K+ current IKr and the human ether‐a go‐go‐related gene (HKRG) K+ channels that underlie it. Astemizole also is rapidly metabolized. The principal metabolite is desmethylastemizole, which retains H1‐receptor antagonist properties, has a long elimination time of 9 to 13 days, and… 
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The anti-malarial drug halofantrine and its metabolite N-desbutylhalofantrine block HERG potassium channels.
Interactions of the antimalarial drug mefloquine with the human cardiac potassium channels KvLQT1/minK and HERG.
TLDR
Inhibition by mefloquine of KvLQT1/minK in the human heart may in part explain the synergistic prolongation of QT interval observed when this drug is coadministered with the HERG antagonist halofantrine.
Clemastine, a conventional antihistamine, is a high potency inhibitor of the HERG K+ channel.
Interactions of the 5-hydroxytryptamine 3 antagonist class of antiemetic drugs with human cardiac ion channels.
TLDR
The antiemetic agents tested in this study block human cardiac Na(+) channels probably by interacting with the inactivated state, which may lead to clinically relevant Na(+ channel blockade, especially when high heart rates or depolarized/ischemic tissue is present.
Mechanism of Block of hEag1 K+ Channels by Imipramine and Astemizole
TLDR
Using inside- and outside-out patch recordings, it is found that a permanently charged, quaternary derivative of imipramine (N-methyl-imipramines) only blocks channels from the intracellular side of the membrane.
Inhibition of hERG K+ currents by antimalarial drugs in stably transfected HEK293 cells.
Cardiac hERG K+ Channel as Safety and Pharmacological Target.
TLDR
A reduction of the hERG/IKr current has been recognized as a predominant mechanism responsible for the drug-induced delayed repolarization known as acquired long QT syndromes (LQTS), which is linked to an increased risk for "torsades de pointes" ventricular arrhythmias and sudden cardiac death.
Blockade of the Human Ether A-Go-Go–Related Gene (hERG) Potassium Channel by Fentanyl
TLDR
Although mechanisms of fentanyl-related sudden death need further investigation, blockade of hERG channels may contribute to the death of individuals with high-concentration overdose or compromised cardiac repolarization.
Flunarizine is a Highly Potent Inhibitor of Cardiac hERG Potassium Current
TLDR
The effects of flunarizine on potassium currents through cardiac channels encoded by the human ether-a-go-go related gene (hERG) stably expressed in CHO cells are examined with standard whole-cell voltage-clamp techniques.
Effect of trazodone on hERG channel current and QT-interval.
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References

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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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