title: Analysis of proarrhythmic potential of antipsychotics risperidone and olanzapine in anesthetized dogs.
abstract: 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.
authors.affiliation: Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ando
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugiyama
authors.forename: Akira
authors.initials: A
authors.lastname: Takahara
authors.forename: Yoshioki
authors.initials: Y
authors.lastname: Satoh
authors.forename: Tomomichi
authors.initials: T
authors.lastname: Ishizaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Keitaro
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: 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
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine