H. Wang, P. Carlier, W. Ho
Mar 1, 1999
Citations
1
Influential Citations
19
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Quality indicators
Journal
Zhongguo yao li xue bao = Acta pharmacologica Sinica
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.