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Effect of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone fumarate, a novel acetylcholinesterase inhibitor, on spatial cognitive impairment induced by chronic cerebral hypoperfusion in rats.

Abstract
It is of interest whether the acetylcholinesterase inhibitor, 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone fumarate (TAK-147), can improve cognitive impairment caused by chronic cerebral ischemia in rats. Two weeks after four-vessel occlusion, apparent impairments of spatial retrieval memory were observed in the Morris water maze. Both TAK-147 at doses of 0.1, 0.3 and 1.0 mg/kg and donepezil at doses of 0.3 and 1.0 mg/kg significantly ameliorated ischemia-induced memory deficits dose-dependently, but tacrine had no appreciable effect. Furthermore, we demonstrate that the intensity of staining by 2,3,5-triphenyltetrazolium in the hippocampal and cortical slices was significantly decreased by ischemia (10 min anoxia/aglycemia), and that it was also significantly restored by treatment with TAK-147 and donepezil.
AuthorsA Jing Xu, Zhong Chen, Kazuhiko Yanai, Yu Wen Huang, Er Qing Wei
JournalNeuroscience letters (Neurosci Lett) Vol. 331 Issue 1 Pg. 33-6 (Oct 04 2002) ISSN: 0304-3940 [Print] Ireland
PMID12359317 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Benzazepines
  • Cholinesterase Inhibitors
  • Coloring Agents
  • Indans
  • Neuroprotective Agents
  • Piperidines
  • Tetrazolium Salts
  • Tacrine
  • triphenyltetrazolium
  • TAK 147
  • Donepezil
Topics
  • Animals
  • Benzazepines (pharmacology)
  • Brain (drug effects)
  • Brain Ischemia (drug therapy, metabolism, physiopathology)
  • Cholinesterase Inhibitors (pharmacology)
  • Coloring Agents
  • Donepezil
  • Dose-Response Relationship, Drug
  • Indans (pharmacology)
  • Male
  • Maze Learning (drug effects)
  • Neuroprotective Agents (pharmacology)
  • Organ Culture Techniques
  • Piperidines (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Tacrine (pharmacology)
  • Tetrazolium Salts

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