Analysis of proarrhythmic potential of antipsychotics risperidone and olanzapine in anesthetized dogs.
In vitro electrophysiological studies have shown that second-generation antipsychotic drugs risperidone and olanzapine inhibit rapidly activating delayed rectifier K(+) currents and prolong action potential duration of the isolated ventricular myocardium. In this study, we analyzed in vivo cardiohemodynamic and electrophysiological profiles of risperidone and olanzapine using the halothane-anesthetized canine model to clarify their proarrhythmic potential. A clinically relevant dose of risperidone (0.03 mg/kg, i.v.) did not affect the ventricular repolarization process, whereas the supra-therapeutic doses (0.3 and 3 mg/kg, i.v.) prolonged the duration of monophasic action potential of the ventricle. Furthermore, the terminal repolarization period, an index of extent of electrical vulnerability, was prolonged after the supra-therapeutic doses. In contrast, therapeutic to supra-therapeutic doses of olanzapine (0.03-3 mg/kg, i.v.) hardly affected the ventricular repolarization process. Therefore, more caution has to be paid on the use of risperidone than olanzapine for patients with risks of the elevated plasma concentration.
Ando
Kentaro
K
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
Sugiyama
Atsushi
A
Takahara
Akira
A
Satoh
Yoshioki
Y
Ishizaka
Tomomichi
T
Nakamura
Yuji
Y
Hashimoto
Keitaro
K
D000200:Action Potentials / Q000187:drug effects; D000758:Anesthesia; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D001569:Benzodiazepines / Q000009:adverse effects / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002036:Bundle of His / Q000187:drug effects / Q000502:physiology; D002302:Cardiac Output; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D000077152:Olanzapine; D018967:Risperidone / Q000009:adverse effects* / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine