Does the sedative agent, JM-1232(-) cause QT prolongation with subsequent torsades de pointes?
AIMS: JM-1232(-) ((-)-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]-2-phenyl-3,5,6,7-tetrahydrocyclopenta[f] isoindole-1(2H)-one) is a novel isoindoline compound that acts on benzodiazepine receptors. Clinical trials are being conducted to assess its potential clinical use as an intravenous anesthetic or sedative agent. In the present study, we investigated the possibility of QT prolongation caused by JM-1232(-). MAIN METHODS: We examined telemetry electrocardiogram (ECG) recordings from unrestrained guinea pigs after intravenous administration of 1, 10, 25 or 50mg/kg of JM-1232(-). We also examined in situ measurements of monophasic action potential duration at 30 and 90% of repolarization (MAP(30) and MAP(90), respectively) and MAP triangulation (MAP(90-30)) from guinea pig hearts that were perfused on a Langendorff apparatus with 0, 0.1, 1, 5, 10 and 20 microg/ml of JM-1232(-). The telemetry ECG recordings showed QTc prolongation 20 min after administration of JM-1232(-) at 50mg/kg. KEY
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