High affinity blockade of the HERG cardiac K(+) channel by the neuroleptic pimozide.

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Kang J, Wang L, Cai F, Rampe D

High affinity blockade of the HERG cardiac K(+) channel by the neuroleptic pimozide.

Eur J Pharmacol. 2000 Mar 31;392(3):137-40.

PubMed ID

10762666 [ View in PubMed

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Abstract

Pimozide is an antipsychotic agent also used to treat facial tics. Pimozide can cause acquired long QT syndrome and ventricular arrhythmias. To elucidate the mechanism behind these clinical findings, we examined the effects of pimozide on the cloned human cardiac K(+) channels HERG (human ether-a-go-go-related gene; rapid component of delayed rectifier), Kv1.5 (ultra-rapid delayed rectifier) and KvLQT1/minK (slow component of delayed rectifier). Using patch clamp electrophysiology, we found that pimozide was a potent inhibitor of HERG displaying an IC(50) value of 18 nM. In contrast, pimozide (10 microM) was a weak inhibitor of KvLQT1/minK and Kv1.5. We conclude that pimozide is a specific, high affinity antagonist of HERG, and that this interaction leads to prolongation of cardiac repolarization.

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