R. Kato, R. Nakano, H. Miki
2010
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Abstract
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 chemical compound that affects benzodiazepine receptors, and is considered for application as a new sedative or intravenous anesthetic agent. To investigate the safety of JM-1232(-), preclinical studies investigating the pharmacokinetics of normaland high-dose JM-1232(-) are needed. In this study, we used high performance liquid chromatography(HPLC) to measure the concentration of JM-1232(-) in plasma, and investigated the pharmacokinetics of lowto high-dose JM-1232(-) in rats. The effects of bolus administration of JM-1232(-)(1, 10, 25, 50, and 75 mg/kg) on the pharmacokinetic parameters were assessed in rats. We extrapolated JM-1232(-) to be a one-compartment model within 60 minutes after bolus administration. In the 50 mg/kg group, a signifi*Laboratory of Clinical Pharmacy and Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sciences, Osaka, Japan **Laboratories of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, Osaka, Japan ***Department of Internal Medicine III, Osaka Medical College, Osaka, Japan cant increase in the elimination rate constant was observed, which is considered to be the saturation of metabolism and/or excretion. The rats were dead in the 75 mg/kg group. Thus, JM-1232(-) administered to rats at doses above 50 mg/kg is likely toxic. Key words; JM-1232(-), sedative agent, assay,