Drug-induced block of cardiac HERG potassium channels and development of torsade de pointes arrhythmias: the case of antipsychotics.
The prolongation of the cardiac repolarization process, a result of the blocking of the Human Ether-ago-go Related Gene potassium channel, is an undesired accessory property shared by many pharmacological classes of non-cardiovascular drugs. Often the delayed cardiac repolarization process can be identified by a prolongation of the QT interval of the electrocardiograph. In these conditions, premature action potentials can trigger a dangerous polymorphic ventricular tachyarrhythmia, known as torsade de pointes, which occasionally can result in lethal ventricular fibrillation. In this work, brief descriptions of the electrophysiological basis of torsade de pointes and of the several pharmacological classes of torsadogenic drugs are given. Attention is focused on antipsychotics, with a deeper overview on the experimental and clinical reports about their torsadogenic properties.
Calderone
Vincenzo
V
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università degli Studi di Pisa, Via Bonanno 6, I-56126, Pisa, Italy. calderone@farm.unipi.it
Testai
Lara
L
Martinotti
Enrica
E
Del Tacca
Mario
M
Breschi
Maria Cristina
MC
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000145:classification / Q000627:therapeutic use; D006801:Humans; D007558:Italy; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000187:drug effects*; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000503:physiopathology
D014150:Antipsychotic Agents; D024642:Potassium Channels, Voltage-Gated