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Risperidone alone did not induce torsade de pointes: Experimental evidence from the chronic atrioventricular block
Yoshio Nunoi1, Koki Chiba2, Mihoko Hagiwara-Nagasawa2
1Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan; Division of Cardiovascular Surgery, Department of Surgery, Faculty of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan.
Abstract:
We assessed torsadogenic action of risperidone, which can potently inhibit IKr as well as α1-adrenoceptor. A toxic dose of 3 mg/kg of risperidone was intravenously administered over 10 min to chronic atrioventricular block dogs without anesthesia with monitoring Holter electrocardiogram (n = 4). Risperidone increased atrial/ventricular rate for 1-12 h/1-6 h and prolonged QTcF at 6 h after its administration, whereas it did not increase short-term variability of repolarization or induced torsade de pointes. These results suggest that α1-adrenoceptor blockade-dependent, hypotension-induced, reflex-mediated increase of sympathetic tone by risperidone might play a role in protecting the heart from IKr inhibition-associated torsade de pointes.
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