In vivo analysis of torsadogenic potential of an antipsychotic drug paliperidone using the acute atrioventricular block rabbit as a proarrhythmia model

We assessed electrophysiological effects of an atypical antipsychotic drug paliperidone in acute atrioventricular block rabbits. intravenous administration of paliperidone at a clinically relevant dose (0.06 mg/kg) hardly affected the qt interval or monophasic action potential (map) duration,and the higher doses (0.6 and 6 mg/kg) prolonged the qt interval and map duration. meanwhile,premature ventricular contractions with r on t phenomenon were observed in 3 out of 6 animals at the middle dose,and torsades de pointes (tdp) episodes were detected in 2 out of 6 animals at the high dose. intravenous administration of its chemically related compound risperidone at a clinically relevant dose (0.03 mg/kg) hardly affected the electrophysiological parameters,and the higher doses (0.3 and 3 mg/kg) prolonged the qt interval and map duration. meanwhile,the premature ventricular contractions with r on t were observed in 2 out of 6 animals at the middle dose,and tdp episodes were detected in 4 out of 6 animals at the high dose. these results suggest that paliperidone showed torsadogenic potential at supra-therapeutic doses,whose potency can be estimated to be equal or slightly subordinate in comparison with that of risperidone. © 2016 the authors