Cellular mechanism of the QT prolongation induced by sulpiride.
In this study, the authors investigated the electrophysiological effect of sulpiride on cardiac repolarization using conventional microelectrode recording techniques in isolated canine Purkinje fibers and a whole-cell patch clamp technique in transiently transfected cells with the hERG, KCNQ1/KCNE1, KCNJ2, and SCN5A cDNA and in rat cardiac myocytes for I(Ca). In studies of action potential duration, 10 microM, 100 microM, 300 microM, and 1 mM sulpiride prolonged action potential duration in a concentration-dependent manner. In studies of cardiac ion channels, sulpiride did not significantly affect I(Na), I(Ca), I(Ks), I(K1), except for I(Kr). Sulpiride dose-dependently decreased the hERG tail current. It is considered that the prolonged action potential duration by sulpiride was mainly the result of inhibition of the hERG channel. The data suggest that the clinical use of sulpiride is reasonable within therapeutic plasma concentrations, but all patients taking this drug should be cautiously monitored for clinical signs of long-QT syndrome and severe arrhythmia.
Lee
Hyang-Ae
HA
Department of pharmacology, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 305-343, Korea. ejkim@kitox.re.kr
Kim
Ki-Suk
KS
Park
Sang-Joon
SJ
Kim
Eun-Joo
EJ
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000633:toxicity*; D014150:Antipsychotic Agents / Q000633:toxicity*; D002460:Cell Line; D004285:Dogs; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D013469:Sulpiride / Q000633:toxicity*
D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D007473:Ion Channels; D015221:Potassium Channels; D013469:Sulpiride