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一种新型认知增强剂,(R)-(-)-1-(苯并[b]噻吩-5-基)-2-[2-(N,N-二乙氨基)乙氧基]乙醇盐酸盐。对脑栓塞和基底前脑损伤所致大鼠记忆障碍的影响。

A new cognition-enhancing agent, (R)-(-)-1-(benzo[b]thiophen-5-yl)- 2-[2-(N,N-diethylamino)ethoxy]ethanol hydrochloride. Effects on memory impairment in rats generated by cerebral embolization and basal forebrain lesions.

作者信息

Ono S, Yamafuji T, Chaki H, Todo Y, Maekawa M, Kitamura K, Kimura T, Nakada Y, Mozumi K, Narita H

机构信息

Research Laboratories, Toyama Chemical Co., Ltd., Japan.

出版信息

Biol Pharm Bull. 1995 Dec;18(12):1779-83. doi: 10.1248/bpb.18.1779.

Abstract

The title compound (T-588) has been evaluated for its ameliorating effect on memory impairment generated by cerebral embolization and by a basal forebrain (BF) lesion in male Wistar rats. The memory and learning deficits induced by injection of carbon-microspheres into the internal carotid artery were significantly improved by T-588 at oral dose of 3-10 mg/kg, as determined by an active avoidance response assay, whereas the reference drugs (tacrine, idebenone and indeloxazine) proved almost inactive in the same assay procedure. As far as the embolization was concerned, a significant decrease in cerebral acetylcholine and monoamines was observed. The effect on the memory impairment caused by an electrolytic lesion of the BF was assessed by a passive avoidance task. T-588 exhibited a bell-shaped dose-response curve and was most active at 1 mg/kg (oral dose), while tacrine showed equal activity at 10 mg/kg.

摘要

已对标题化合物(T - 588)改善雄性Wistar大鼠脑栓塞和基底前脑(BF)损伤所致记忆障碍的作用进行了评估。通过主动回避反应试验测定,口服剂量为3 - 10 mg/kg的T - 588可显著改善经颈内动脉注射碳微球诱导的记忆和学习缺陷,而在相同试验过程中,参比药物(他克林、艾地苯醌和茚洛秦)几乎无活性。就栓塞而言,观察到脑内乙酰胆碱和单胺显著减少。通过被动回避任务评估T - 588对BF电解损伤所致记忆障碍的影响。T - 588呈现钟形剂量反应曲线,口服剂量为1 mg/kg时活性最强,而他克林在10 mg/kg时显示同等活性。

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