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乙酰胆碱酯酶抑制剂分析:生物分析、降解与代谢

Analysis of acetylcholinesterase inhibitors: bioanalysis, degradation and metabolism.

作者信息

Azevedo Marques Lygia, Giera Martin, Lingeman Henk, Niessen Wilfried Ma

机构信息

VU University Amsterdam, Faculty of Sciences, BioMolecular Analysis group, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.

出版信息

Biomed Chromatogr. 2011 Jan;25(1-2):278-99. doi: 10.1002/bmc.1573. Epub 2010 Dec 10.

DOI:10.1002/bmc.1573
PMID:21154892
Abstract

Alzheimer's is a neurodegenerative disease. Its symptoms are attributed to a deficiency of cholinergic neurotransmission. The drugs of choice for the treatment of Alzheimer's disease are acetylcholinesterase (AChE) inhibitors. Starting in the 1980's from non-specific AChE inhibitors, the first-generation drugs such as physostigmine, a second generation of more selective and better tolerated products has been developed. Methods to detect and quantify these drugs and their metabolites in biological samples have been developed for analysis in plasma, blood, urine and cerebrospinal fluid. Diverse detection techniques have been used, such as ultraviolet, fluorescence, electrochemical and mass spectrometry. In this review, the methods applied to the analysis of these drugs and their metabolites in different biological matrices are reviewed and discussed. The stability of these drugs in biological matrices and under stress-conditions is also included in the discussion.

摘要

阿尔茨海默病是一种神经退行性疾病。其症状归因于胆碱能神经传递不足。治疗阿尔茨海默病的首选药物是乙酰胆碱酯酶(AChE)抑制剂。从20世纪80年代的非特异性AChE抑制剂开始,已开发出第一代药物,如毒扁豆碱,随后又开发出了第二代更具选择性且耐受性更好的产品。已经开发出在生物样品中检测和定量这些药物及其代谢物的方法,用于血浆、血液、尿液和脑脊液的分析。已使用了多种检测技术,如紫外、荧光、电化学和质谱分析。在本综述中,将对应用于不同生物基质中这些药物及其代谢物分析的方法进行综述和讨论。这些药物在生物基质中和应激条件下的稳定性也将在讨论中涉及。

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Analysis of acetylcholinesterase inhibitors: bioanalysis, degradation and metabolism.乙酰胆碱酯酶抑制剂分析:生物分析、降解与代谢
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[Cholinergic deficiency syndrome as an indicator for the cholinesterase inhibitors].[胆碱能缺乏综合征作为胆碱酯酶抑制剂的指标]
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Sensitivity of butyrylcholinesterase knockout mice to (--)-huperzine A and donepezil suggests humans with butyrylcholinesterase deficiency may not tolerate these Alzheimer's disease drugs and indicates butyrylcholinesterase function in neurotransmission.丁酰胆碱酯酶基因敲除小鼠对(-)-石杉碱甲和多奈哌齐的敏感性表明,丁酰胆碱酯酶缺乏的人可能无法耐受这些治疗阿尔茨海默病的药物,并提示丁酰胆碱酯酶在神经传递中的作用。
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[Neurotransmitters in Alzheimer's disease].[阿尔茨海默病中的神经递质]
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