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.

Abstract

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 mg.kg-1, 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 mumol.kg-1, i.g. or i.p.) to shorten the escape latency was 24 or 12 times of tacrine (8.52 mumol.kg-1 i.g., 4.26 mumol.kg-1 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

Substances

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