AIM To evaluate effect of TAK-147 on spatial memory deficit induced by scopolamine. METHODS Morris water maze was used to measure spatial memory in rats and open field test was used to analyse locomotor activity. RESULTS In the acquisition memory process, scopolamine (0.4 mg/kg, ip) markedly increased the escape latency to the platform. Ip injection of both TAK-147 and donepezil ameliorated scopolamine-induced deficit, dose-related and significant effect was obtained at doses of 0.1-1.0 mg/kg. In the memory retrieval process, increased latency induced by scopolamine (1.5 mg/kg, ip) was also significantly reversed by treatment with TAK-147 (0.1, 0.3, and 1.0 mg/kg), donepezil (0.3 and 1.0 mg/kg), and tacrine (3 and 5 mg/kg), respectively. TAK-147 has a little potent efficacy to donepezil, and was more potent than tacrine. In the locomotor test, both TAK-147 and donepizil created no appreciable change of locomotor activities, compared with scopolamine or saline. CONCLUSION TAK-147 plays an important role in spatial cognition, and this result provides additional evidence that TAK-147 is an ideal AChE inhibitor and is useful for the treatment of Alzheimer's disease.

中文翻译：

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TAK-147逆转东pol碱诱导的大鼠空间记忆障碍。

目的评估TAK-147对东pol碱诱导的空间记忆障碍的作用。方法采用莫里斯水迷宫测量大鼠的空间记忆，并采用开放视野试验分析运动能力。结果在采集记忆过程中，东pol碱（0.4 mg / kg，ip）明显增加了平台逃逸的潜伏时间。TAK-147和多奈哌齐的IP注射在0.1-1.0 mg / kg的剂量下改善了东pol碱所致的赤字，剂量相关和显着的作用。在记忆检索过程中，用TAK-147（0.1、0.3和1.0 mg / kg），多奈哌齐（0.3和1.0 mg / kg）治疗也可以明显逆转东pol碱（1.5 mg / kg，腹膜内）引起的潜伏期延长。和他克林（分别为3和5 mg / kg）。TAK-147对多奈哌齐的作用较小，并且比他克林更有效。在运动测试中，与东pol碱或生理盐水相比，TAK-147和多奈哌齐均未引起运动活动的明显改变。结论TAK-147在空间认知中起着重要作用，这一结果提供了更多的证据，表明TAK-147是理想的AChE抑制剂，可用于治疗阿尔茨海默氏病。