Korean J Physiol Pharmacol.  2010 Oct;14(5):305-310. 10.4196/kjpp.2010.14.5.305.

Response of I(Kr) and hERG Currents to the Antipsychotics Tiapride and Sulpiride

Affiliations
  • 1Department of Physiology, Institute of Bioscience and Biotechnology, Kangwon National University School of Medicine, Chuncheon 200-701, Korea. suhyunjo@kangwon.ac.kr
  • 2Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, Korea.

Abstract

The human ether-a-go-go-related gene (hERG) channel is important for repolarization in human myocardium and is a common target for drugs that prolong the QT interval. We studied the effects of two antipsychotics, tiapride and sulpiride, on hERG channels expressed in Xenopus oocytes and also on delayed rectifier K+ currents in guinea pig cardiomyocytes. Neither the amplitude of the hERG outward currents measured at the end of the voltage pulse, nor the amplitude of hERG tail currents, showed any concentration-dependent changes with either tiapride or sulpiride (3~300 micrometer). However, our findings did show that tiapride increased the potential for half-maximal activation (V(1/2)) of HERG at 10~300 micrometer, whereas sulpiride increased the maximum conductance (G(max)) at 3, 10 and 100 micrometer. In guinea pig ventricular myocytes, bath applications of 100 and 500 micrometer tiapride at 36degrees C blocked rapidly activating delayed rectifier K+ current (I(Kr)) by 40.3% and 70.0%, respectively. Also, sulpiride at 100 and 500 micrometer blocked I(Kr) by 38.9% and 76.5%, respectively. However, neither tiapride nor sulpiride significantly affected the slowly activating delayed rectifier K+ current (I(Ks)) at the same concentrations. Our findings suggest that the concentrations of the antipsychotics required to evoke a 50% inhibition of IKr are well above the reported therapeutic plasma concentrations of free and total compound.

Keyword

hERG channel; Rapidly-activating delayed rectifier K+ channel; Slowly-activating delayed rectifier K+ channel; Sulpiride; Tiapride

MeSH Terms

Animals
Antipsychotic Agents
Baths
Guinea Pigs
Humans
Muscle Cells
Myocardium
Myocytes, Cardiac
Oocytes
Plasma
Sulpiride
Tiapride Hydrochloride
Xenopus
Antipsychotic Agents
Sulpiride
Tiapride Hydrochloride
Full Text Links
  • KJPP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2022 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr