Cardiovascular responses to intravenous injection of a novel isoindolin-1-one derivate in conscious rats
| Autor: | Isao Tsuneyoshi, Takato Kunitake, Tetsuro Shirasaka |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Atropine
Flumazenil Male Mean arterial pressure medicine.medical_specialty Sympathetic Nervous System Time Factors Baroreceptor Narcotic Antagonists Adrenergic beta-Antagonists Blood Pressure Propranolol Isoindoles Baroreflex Piperazines chemistry.chemical_compound Catecholamines Catheters Indwelling Heart Conduction System Heart Rate Internal medicine Animals Medicine Rats Wistar GABA Modulators Molecular Biology Sinoatrial Node Analysis of Variance Dose-Response Relationship Drug Naloxone business.industry General Neuroscience Parasympatholytics Rats Endocrinology chemistry Catecholamine Hexamethonium Neurology (clinical) business Developmental Biology medicine.drug |
| Zdroj: | Brain Research. 1300:105-113 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2009.08.092 |
| Popis: | 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 acidA (GABAA) 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–GABAA receptors. |
| Databáze: | OpenAIRE |
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