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

被引:45
作者
Liu, J
Ho, WL
Lee, NTK
Carlier, PR
Pang, YP
Han, YF
机构
[1] Hong Kong Univ Sci & Technol, Dept Biochem, Hong Kong, Hong Kong, Peoples R China
[2] Hong Kong Univ Sci & Technol, Dept Chem, Hong Kong, Hong Kong, Peoples R China
[3] Mayo Clin & Mayo Fdn, Dept Pharmacol, Ctr Canc, Rochester, MN 55905 USA
关键词
bis(7)-tacrine; AF64A; cholinesterase inhibitors; water maze; Alzheimer's disease;
D O I
10.1016/S0304-3940(00)00905-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The novel dimer bis(7)-tacrine (1,7-N-Heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacrindine), 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 mu mol/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. All rights reserved.
引用
收藏
页码:165 / 168
页数:4
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