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

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 micromol/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.

• Authors: J Liu, W Ho, N T Lee, P R Carlier, Y Pang, Y Han
• Journal: Neuroscience letters (Neurosci Lett) Vol. 282 Issue 3 Pg. 165-8 (Mar 24 2000) ISSN: 0304-3940 [Print] Ireland
• PMID: 10717417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine
• Aziridines
• Cholinesterase Inhibitors
• Toxins, Biological
• Tacrine
• ethylcholine aziridinium
• Choline

Topics

• Animals
• Aziridines (administration & dosage)
• Choline (administration & dosage, analogs & derivatives)
• Cholinesterase Inhibitors (pharmacology)
• Escape Reaction (drug effects)
• Injections, Intraventricular
• Male
• Maze Learning (drug effects)
• Memory (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reaction Time (drug effects)
• Tacrine (analogs & derivatives, pharmacology)
• Toxins, Biological (administration & dosage)