Bis(7)-tacrine, a novel acetylcholinesterase inhibitor, reverses AF64A- induced deficits in navigational memory in rats

Jing Liu, Wing Lok Ho, Nelson Tze Kin Lee, Paul R. Carlier, Yuan Ping Pang, Yi Fan Han

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

The novel dimer bis(7)-tacrine (1,7-N-Heptylene-bis-9,9'-amino-1,2,3,4- tetrahydroacridine), which exhibits higher potency, selectivity and oral activity on acetylcholinesterase inhibition in vivo than tacrine, was evaluated for its ability to reverse AF64A-induced spatial memory impairment in rats using the Morris water maze. The intracerebroventricular injection of AF64A (3 nmol/side) resulted in a substantial increase in the escape latency to find the platform (F(1,7) = 30.2, P < 0.01). The observed impairment of spatial memory was paralleled by a 47% decrease in choline acetyltransferase activity in the hippocampus. Oral administration of bis(7)-tacrine (0.22-0.89 μmol/kg) dose-dependently reversed the AF64A-induced latency delay to the level of the saline control group (F(4,28) = 7.45, P < 0.05). The present study provides additional evidence of bis(7)-tacrine as an ideal candidate for the palliative treatment of Alzheimer's disease. (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)165-168
Number of pages4
JournalNeuroscience Letters
Volume282
Issue number3
DOIs
StatePublished - Mar 24 2000

Keywords

  • AF64A
  • Alzheimer's disease
  • Bis(7)-tacrine
  • Cholinesterase inhibitors
  • Water maze

ASJC Scopus subject areas

  • Neuroscience(all)

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