• Tetsuro Shirasaka, Takato Kunitake, and Isao Tsuneyoshi.
• Department of Anesthesiology and Intensive Care, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. shirasak@med.miyazaki-u.ac.jp
• Brain Res. 2009 Dec 1; 1300: 105-13.

AbstractAn isoindolin-1-one derivate, JM-1232(-), was recently developed as a sedative and hypnotic agent with a strong affinity for the central benzodiazepine binding site of gamma-aminobutyric acid(A) (GABA(A)) receptors. The purpose of this study was to examine the effects of JM-1232(-) on the cardiovascular and sympathetic functions of conscious rats. We investigated the effect of JM-1232(-) on the mean arterial pressure (MAP), heart rate (HR), baroreflex activity, and plasma catecholamine levels in conscious rats. The intravenous (i.v.) administration of JM-1232(-) (0.1, 0.3, and 1.0 mg/kg/min) for 20 min decreased MAP and increased HR in intact rats. In sinoaortic denervated (SAD) rats, JM-1232(-) decreased MAP and HR. A decrease in MAP induced by JM-1232(-) was prevented by pre-treatment with hexamethonium and enhanced by SAD. An increase in HR induced by JM-1232(-) was prevented by pre-treatment with atropine, propranolol, or hexamethonium. A decrease in MAP and an increase in HR induced by JM-1232(-) were antagonized by co-administration of flumazenil. A high dose of JM-1232(-) decreased the plasma norepinephrine concentration, and a subdepressor dose of JM-1232(-) did not affect the baroreceptor reflex. These results show that the i.v. administration of JM-1232(-) decreased MAP mediated by benzodiazepine-GABA(A) receptors.

45 keywords...

hide…