Reversal of scopolamine-induced spatial memory deficits in rats by TAK-147.
OBJECTIVE
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.


CONCLUSIONS
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.
Chen
Zhong
Z
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310006, China. chenzfl@hotmail.com
Xu
A-Jing
AJ
Li
Ren
R
Wei
Er-Qing
EQ
D000818:Animals; D001552:Benzazepines / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D007189:Indans / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine; D013619:Tacrine / Q000494:pharmacology / Q000627:therapeutic use
D001552:Benzazepines; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D013619:Tacrine; C099872:TAK 147; D000077265:Donepezil; D012601:Scopolamine