标题：Saturation Pharmacokinetics of Sedative Agent, JM-1232(−)((−)-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]-2-phenyl-3,5,6,7-tetrahydrocyclopenta[f] isoindole-1(2H)-one) at High-Dose in Rats
出版社：Japan Society of Circulation Control in Medicine
摘要：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 normal- and 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 low- to 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 significant 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.
