Attenuation of scopolamine-induced deficits in navigational memory performance in rats by bis(7)-tacrine, a novel dimeric AChE inhibitor

Zhongguo Yao Li Xue Bao. 1999 Mar;20(3):211-7.


Aim: To study the effects of 1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine [bis(7)-tacrine], a novel dimeric acetylcholine-sterase inhibitor (AChEI) derived from 9-amino-1,2,3,4-tetrahydroaminoacridine (tacrine), on scopolamine-induced spatial memory impairment.

Methods: The effects of bis(7)-tacrine were investigated on the 5-d performance of young adult rats in the Morris water maze. The latency to find the platform in the water maze was measured to evaluate performance. Tacrine was used as a reference drug.

Results: Scopolamine (0.3, i.p.) resulted in an increase in latency period (> 100% increase) as compared with saline treated controls. Both bis(7)-tacrine and tacrine lessened the increased latency induced by scopolamine to the level of saline control group. The relative potency of bis(7)-tacrine (0.35, i.g. or i.p.) to shorten the escape latency was 24 or 12 times of tacrine (8.52 i.g., 4.26 i.p.) following i.g. or i.p. administration, respectively. There appeared to be an inverse bell-shape dose-dependent effect for both compounds tested.

Conclusion: Bis(7)-tacrine is a more potent and orally active AChEI than tacrine, and has potential for the palliative treatment of Alzheimer disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholinesterase Inhibitors / pharmacology*
  • Male
  • Maze Learning / drug effects*
  • Memory / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Scopolamine
  • Tacrine / analogs & derivatives*
  • Tacrine / pharmacology


  • 1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine
  • Cholinesterase Inhibitors
  • Tacrine
  • Scopolamine