摘要
目的：研究他克林的双体衍生物双（７）他克林对东莨菪碱引起的大鼠记忆障碍的影响．方法：采用大鼠Ｍｏｒｉｓ水迷宫固定平台的程序研究空间记忆．以他克林为对照药．结果：东莨菪碱（０３ｍｇ·ｋｇ－１，ｉｐ）使大鼠到达平台的潜伏期明显长于生理盐水对照组．双（７）他克林（０３５μｍｏｌ·ｋｇ－１，ｉｇ或ｉｐ）和他克林（８５２μｍｏｌ·ｋｇ－１ｉｇ；４２６μｍｏｌ·ｋｇ－１ｉｐ）均可对抗东莨菪碱导致的空间记忆障碍；在灌胃及腹腔注射途径下，双（７）他克林的效价，分别强于他克林２４及１２倍．结论：双（７）他克林明显改善东莨菪碱导致的空间记忆障碍，其作用强于他克林．
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 acetyl￣choline￣sterase inhibitor (AChEI) derived from 9 amino 1,2,3,4 tetrahydroaminoacridine (tacr￣ine), 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: Scopo￣la￣mine (0 3 mg·kg -1 , ip) 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 μmol·kg -1 , ig or ip) to shorten the escape latency was 24 or 12 times of tacrine (8 52 μmol·kg -1 ig, 4 26 μmol·kg -1 ip) following ig or ip administration, respec￣tive￣ly. 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.
出处
《中国药理学报》
CSCD
1999年第3期211-217,共7页
Acta Pharmacologica Sinica
关键词
胆碱酯酶抑制剂
他克林
东莨菪碱
早老性痴呆
cholinesterase inhibitors
tacrine
bis(7) tacrine
memory
Morris water maze
scopolamine
Alzheimer disease
