Ono S, Yamafuji T, Chaki H, Todo Y, Maekawa M, Kitamura K, Kimura T, Nakada Y, Mozumi K, Narita H
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Biol Pharm Bull. 1995 Dec;18(12):1779-83. doi: 10.1248/bpb.18.1779.
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.
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。