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Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium
Benoit Drolet1, Tao Yang, Pascal Daleau
1Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, U.S.A.
Journal of Cardiovascular Pharmacology
|May 31, 2003
Summary
Risperidone, a common neuroleptic, may prolong cardiac repolarization and block potassium channels, increasing arrhythmia risk. These effects, observed at therapeutic levels, are concerning for specific patient groups.
Area of Science:
- Cardiology
- Pharmacology
- Electrophysiology
Background:
- Risperidone, a widely used neuroleptic, has been linked to QT prolongation and sudden death.
- Hypokalemia is a known factor, but potential direct electrophysiologic effects of risperidone were investigated.
Purpose of the Study:
- To investigate the electrophysiologic effects of risperidone on cardiac repolarization.
- To determine if risperidone directly affects ion channels involved in cardiac action potentials.
Main Methods:
- Isolated guinea pig hearts were used to measure action potential duration.
- HERG-transfected cells assessed the effect of risperidone on the I(Kr) potassium current.
Main Results:
- Risperidone prolonged cardiac repolarization in guinea pig hearts.
- Risperidone demonstrated a concentration-dependent block of the I(Kr) current in HERG cells (IC50 = 261 nM).
- No significant block of I(Ks) was observed.
Conclusions:
- Risperidone exhibits Class III antiarrhythmic-like effects by prolonging repolarization and blocking I(Kr) at clinically relevant concentrations.
- These findings suggest a direct proarrhythmic risk associated with risperidone, particularly in patients with CYP2D6 variations or drug interactions.