[Blockade of HERG K+ channels expressed in Xenopus oocytes by antipsychotic agents].

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Osypenko VM, Degtiar VIe, Naid'onov VG, Shuba IaM

[Blockade of HERG K+ channels expressed in Xenopus oocytes by antipsychotic agents].

Fiziol Zh. 2001;47(1):17-25.

PubMed ID

11296551 [ View in PubMed

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Abstract

We have investigated the effects of neuroleptic agents, haloperidol, pimozide and fluspirilen, that are used in clinics to treat psychiatric disorders, but reportedly have proarrhythmic side effects, on HERG-encoded K+ channels responsible for the rapid component of cardiac delayed rectifier K+ current, IKr. All three agents blocked HERG-directed IKr in Xenopus oocytes in a voltage-dependent manner. The extent of the blockade increased with depolarization correlating with channels activation consistent with open-channel blocking mechanism. The IC50 values for the haloperidol-, pimozide- and fluspirilen-induced blockade of fully activated IKr were 1.36, 1.74 and 2.34 mcM respectively. Neuroleptics did not affect the HERG channels steady-state activation and inactivation properties. Thus, the blockade of HERG channels may underly proarrhythmic actions of neuroleptics resulting in a slowing down of the repolarization phase of cardiac action potential, and prolongation of the electrocardiographic QT interval.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pimozide	Potassium voltage-gated channel subfamily H member 2	Protein	Humans	Yes	Inhibitor	Details