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Korean J Physiol Pharmacol
2010 Oct 01;145:305-10. doi: 10.4196/kjpp.2010.14.5.305.
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Response of i(kr) and HERG currents to the antipsychotics tiapride and sulpiride.
Jo SH
,
Lee SY
.
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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 hERGtail currents, showed any concentration-dependent changes with either tiapride or sulpiride (3~300 µM). However, our findings did show that tiapride increased the potential for half-maximal activation (V(1/2)) of HERG at 10~300 µM, whereas sulpiride increased the maximum conductance (G(max)) at 3, 10 and 100 µM. In guinea pig ventricular myocytes, bath applications of 100 and 500 µM tiapride at 36℃ blocked rapidly activating delayed rectifier K(+) current (I(Kr)) by 40.3% and 70.0%, respectively. Also, sulpiride at 100 and 500 µM 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 I(Kr) are well above the reported therapeutic plasma concentrations of free and total compound.
Abbott,
MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia.
1999, Pubmed,
Xenbase
Abbott,
MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia.
1999,
Pubmed
,
Xenbase
Bressolle,
Sulpiride pharmacokinetics in humans after intramuscular administration at three dose levels.
1984,
Pubmed
Capel,
Overdose profiles of new antipsychotic agents.
2000,
Pubmed
Choi,
Inhibition of human ether-a-go-go-related gene K+ channel and IKr of guinea pig cardiomyocytes by antipsychotic drug trifluoperazine.
2005,
Pubmed
,
Xenbase
Curtis,
Prescription of QT-prolonging drugs in a cohort of about 5 million outpatients.
2003,
Pubmed
Heath,
Separation of the components of the delayed rectifier potassium current using selective blockers of IKr and IKs in guinea-pig isolated ventricular myocytes.
1996,
Pubmed
Hennessy,
Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data.
2002,
Pubmed
Huang,
Sulpiride induced torsade de pointes.
2007,
Pubmed
Iglesias,
Tiapride-induced torsade de pointes.
2000,
Pubmed
Ito,
Inhibition by antipsychotic drugs of L-type Ca2+ channel current in PC12 cells.
1996,
Pubmed
Kiehn,
Molecular physiology and pharmacology of HERG. Single-channel currents and block by dofetilide.
1996,
Pubmed
,
Xenbase
Lee,
Cellular mechanism of the QT prolongation induced by sulpiride.
2009,
Pubmed
Lenhard,
The importance of pharmacokinetic data on sulpiride: results of a bioequivalence study of two sulpiride 200 mg preparations following oral administration.
1991,
Pubmed
Lin,
Predictive factors for QTc prolongation in schizophrenic patients taking antipsychotics.
2004,
Pubmed
Madeja,
Follicular tissues reduce drug effects on ion channels in oocytes of Xenopus laevis.
1997,
Pubmed
,
Xenbase
Malik,
Problems of heart rate correction in assessment of drug-induced QT interval prolongation.
2001,
Pubmed
Malik,
Evaluation of drug-induced QT interval prolongation: implications for drug approval and labelling.
2001,
Pubmed
Mucci,
Levosulpiride: a review of its clinical use in psychiatry.
1995,
Pubmed
Nakazawa,
Characterization of inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current in rat phaeochromocytoma cells.
1995,
Pubmed
Ray,
Antipsychotics and the risk of sudden cardiac death.
2001,
Pubmed
Redfern,
Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development.
2003,
Pubmed
Reilly,
Thioridazine and sudden unexplained death in psychiatric in-patients.
2002,
Pubmed
Sanguinetti,
Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents.
1990,
Pubmed
Silvestre,
Comparative evaluation of hERG potassium channel blockade by antipsychotics.
2007,
Pubmed
Steele,
Tiapride. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in geriatric agitation.
1993,
Pubmed
Straus,
Antipsychotics and the risk of sudden cardiac death.
2004,
Pubmed
Stöllberger,
Antipsychotic drugs and QT prolongation.
2005,
Pubmed
Su,
A pilot cross-over design study on QTc interval prolongation associated with sulpiride and haloperidol.
2003,
Pubmed
Sugiyama,
Torsadegenic action of the antipsychotic drug sulpiride assessed using in vivo canine models.
2002,
Pubmed
Thomas,
High-affinity blockade of human ether-a-go-go-related gene human cardiac potassium channels by the novel antiarrhythmic drug BRL-32872.
2001,
Pubmed
,
Xenbase
Tie,
The heart of psychotropic drug therapy.
2000,
Pubmed
Zhou,
Properties of HERG channels stably expressed in HEK 293 cells studied at physiological temperature.
1998,
Pubmed
