Long-lasting antiamnesic effect of a novel anticholinesterase inhibitor (MF268)
Long-lasting antiamnesic effect of a novel anticholinesterase inhibitor (MF268)
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DOI：
10.1016/s0091-3057(97)00526-1
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发表时间：
1998-04-01
影响因子：
3.6
通讯作者：
Sala, M
中科院分区：
文献类型：
--
作者：
Braida, D;Paladini, E;Sala, M
在本研究中，在八臂放射状迷宫中研究了东莨菪碱诱导的大鼠遗忘的短期（120 min）和长期（360 min）拮抗作用，（3a S，8a R）-1，2，3，3a，8，8a-六氢-1，3a，8-三甲基吡咯并[2，3-B]吲哚-5-醇[8（顺式-2，6-二甲基-吗啉-4-基）辛基]-氨基甲酸酯L-重酒石酸盐水合物（MF 268），一种新的胆碱酯酶抑制剂。在完成训练期后，在SC注射东莨菪碱（0.25mg/kg）之前60分钟，向大鼠口服施用增加剂量的MF 268（2; 3、6、7和8 mg/kg）。再过60分钟后，将大鼠置于迷宫中。东莨菪碱诱导的损伤逆转的特征为倒U形剂量-反应曲线，错误次数显著减少，在6 mg/kg剂量下观察到完成迷宫所需的时间。该化合物改善了记忆力，而不影响东莨菪碱诱导的运动过度。当在试验前360分钟给予相同剂量时，观察到健忘动物的数量显著减少，而当在试验前360分钟给予1-苄-4-[（5，6-二甲氧基-1-茚满酮）-2-基]-甲基哌啶盐酸盐（E2020）（0.25 mg/kg）或他克林（0.5 mg/kg）时，未检测到认知改善。全脑胆碱酯酶的动力学证实了MF 268的持久活性。建议在AD治疗中使用MF 268的临床相关性。(C)1998年爱思唯尔科学公司
In the present study a short (120 min) and long-lasting (360 min) antagonism of scopolamine-induced amnesia in rats was investigated in an eight-arm radial maze, by (3a S, 8a R)-1,2,3,3a,8,8a-hexahyrdro-1,3a,8-trimethylpyrrolo [2,3-b]indol-5-ol[8(cis2,6-dimethyl-morpholin-4-yl)octyl]-c arbamate L-bilartrate hydrate (MF268), a new cholinesterase inhibitor. Upon completing the training session, the rats were orally administered increasing doses of MF268 (2; 3, 6, 7, and 8 mg/kg) 60 min prior to SC injection of scopolamine (0.25 mg/kg). Following a further 60 min the rat was placed in the maze. The reversal of scopolamine-induced impairment was characterized by an inverted U-shaped dose-response curve, a significant reduction in the number of errors, and time taken to complete the maze was observed with a dose of 6 mg/kg. The compound improved memory retention without affecting scopolamine-induced hypermotility. When the same dose was administered 360 min prior to the test a significant reduction in the number of amnesic animals was observed, whereas no cognitive improvement was detected when either 1-Benzil-4-[(5,6-dimethoxy-1-indanon)-2-yl]-methyl piperidine hydrochloride (E2020) (0.25 mg/kg) or tacrine (0.5 mg/kg) were administered 360 min prior to the test. The kinetics of whole-brain cholinesterase confirmed the long-lasting activity for MF268. A clinical relevance for the use of MF268 in AD treatment is suggested. (C) 1998 Elsevier Science Inc.