tak-147 and Memory-Disorders

To investigate the influence of chronic epilepsy on spatial memory retrieval in rats, and to evaluate the effects of TAK-147, an acetylcholinesterase inhibitor, and histidine, the precursor of histamine, on the amnesia induced by epilepsy.. After successfully trained in the 8-arm (4-arm baited) radial maze, the rats were ip injected with a subconvulsive dose of pentylenetetrazole (PTZ) every 48 h until fully kindled. Memory retrieval was tested at the same maze.. Impairment of memory retrieval was in a steady state 1 to 18 days after fully kindled, the ability of memory retrieval returned to the control level 31 days after fully kindled. TAK-147 showed an ameliorating effect on memory impairment induced by epilepsy, including reference and working memory in a dose-dependent manner. Histidine only ameliorated reference but not working memory.. PTZ-kindled seizure impair spatial memory retrieval, which it might be due to a decrease of brain acetylcholine and histamine induced by epilepsy.

Topics: Animals; Benzazepines; Chronic Disease; Dose-Response Relationship, Drug; Epilepsy; Male; Maze Learning; Memory Disorders; Pentylenetetrazole; Rats; Rats, Sprague-Dawley

To evaluate effect of TAK-147 on spatial memory deficit induced by scopolamine.. Morris water maze was used to measure spatial memory in rats and open field test was used to analyse locomotor activity.. 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.. 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.

Topics: Animals; Benzazepines; Cholinesterase Inhibitors; Donepezil; Indans; Male; Maze Learning; Memory Disorders; Motor Activity; Piperidines; Rats; Rats, Sprague-Dawley; Scopolamine; Tacrine