Inhibition of human cholinesterases by drugs used to treat Alzheimer disease
Inhibition of human cholinesterases by drugs used to treat Alzheimer disease
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DOI：
10.1097/00002093-200304000-00011
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发表时间：
2003-04-01
影响因子：
2.1
通讯作者：
Martin, E
中科院分区：
文献类型：
--
作者：
Darvesh, S;Walsh, R;Martin, E
目前治疗阿尔茨海默病的认知和行为症状的方法强调使用胆碱酯酶抑制剂。考察了胆碱酯酶抑制剂多奈哌齐、加兰他敏、三氟膦酸盐、毒豆碱、利瓦斯汀和四氢胺吖啶对人乙酰胆碱酯酶（AChE）和人丁基胆碱酯酶（BuChE）的酯酶和芳酰酰基酰胺酶活性的动力学效应。这些药物对AChE和BuChE均有抑制作用，但抑制程度不同。当以神经递质乙酰胆碱的类似物乙酰硫代胆碱代替丁基硫代胆碱作为底物时，这些化合物对BuChE的抑制作用大致相同，甚至更好。此外，这些药物对芳基酰基酰胺酶活性的抑制与对AChE和BuChE酯酶活性的抑制相似。鉴于目前用于治疗阿尔茨海默病的药物同时抑制AChE和BuChE，开发针对单独抑制一种或另一种胆碱酯酶的药物对于理解抑制BuChE和AChE在治疗阿尔茨海默病中的相对重要性可能很重要。
Current approaches to the treatment of cognitive and behavioral symptoms of Alzheimer disease emphasize the use of cholinesterase inhibitors. The kinetic effects of the cholinesterase inhibitors donepezil, galantamine, metrifonate, physostigmine, rivastigmine, and tetrahydroaminoacridine were examined with respect to their action on the esterase and aryl acylamidase activities of human acetylcholinesterase (AChE) and human butyrylcholinesterase (BuChE). Each of these drugs inhibited both AChE and BuChE, but to different degrees. Inhibition of BuChE by these compounds was approximately the same, or better, when acetylthiocholine, the analog of the neurotransmitter acetylcholine, was used as the substrate, instead of butyrylthiocholine. In addition, for these drugs, the inhibition of aryl acylamidase activity paralleled that observed for inhibition of esterase activity of AChE and BuChE. Given that drugs that are currently in use for the treatment of Alzheimer disease inhibit both AChE and BuChE, the development of drugs targeted toward the exclusive inhibition of one or the other cholinesterase may be important for understanding the relative importance of inhibition of BuChE and AChE in the treatment of this disease.