title: Cardiovascular responses to intravenous injection of a novel isoindolin-1-one derivate in conscious rats.
abstract: An 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.
authors.affiliation: Department of Anesthesiology and Intensive Care, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. shirasak@med.miyazaki-u.ac.jp
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shirasaka
authors.forename: Takato
authors.initials: T
authors.lastname: Kunitake
authors.forename: Isao
authors.initials: I
authors.lastname: Tsuneyoshi
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood*; D002408:Catheters, Indwelling; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D054833:Isoindoles / Q000008:administration & dosage*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012849:Sinoatrial Node / Q000187:drug effects / Q000294:innervation; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013997:Time Factors
chemical_list: C534223:3-(2-(4-methyl-1-piperazinyl)-2-oxoethyl)-2-phenyl-3,5,6,7-tetrahydrocyclopenta(f)isoindol-1(2H)-one; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D018757:GABA Modulators; D054833:Isoindoles; D009292:Narcotic Antagonists; D010276:Parasympatholytics; D010879:Piperazines; D009270:Naloxone; D005442:Flumazenil; D001285:Atropine; D011433:Propranolol