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乙酰胆碱酯酶抑制剂在阿尔茨海默病治疗中的应用是否会导致抑郁?

Does the application of acetylcholinesterase inhibitors in the treatment of Alzheimer's disease lead to depression?

机构信息

Department of Molecular Biology and Endocrinology, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.

Department of Physical Chemistry, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.

出版信息

Expert Opin Drug Metab Toxicol. 2021 Jul;17(7):841-856. doi: 10.1080/17425255.2021.1931681. Epub 2021 Jun 10.

Abstract

: Alzheimer's disease and depression are health conditions affecting millions of people around the world. Both are strongly related to the level of the neurotransmitter acetylcholine. Since cholinergic deficit is characteristic of Alzheimer's disease, acetylcholinesterase inhibitors are applied as relevant drugs for the treatment of this disease, elevating the level of acetylcholine. On the other hand, a high level of acetylcholine is found to be associated with the symptoms of clinical depression.: This article aims to discuss if acetylcholinesterase inhibitors used as anti-Alzheimer's drugs could be the cause of the symptoms of clinical depression often linked to this neurological disorder. Emphasis will be put on drugs currently in use and on newly investigated natural products, which can inhibit AChE activity.: Currently, it is not proven that the patient treated for Alzheimer's disease is prone to increased risk for depression due to the acetylcholinesterase inhibition, but there are strong indications. The level of acetylcholine is not the only factor in highly complicated diseases like AD and depression. Still, it needs to be considered isolated, keeping in mind the nature of presently available therapy, especially during a rational drug design process.

摘要

阿尔茨海默病和抑郁症是影响全球数百万人的健康状况。两者都与神经递质乙酰胆碱的水平密切相关。由于胆碱能缺陷是阿尔茨海默病的特征,乙酰胆碱酯酶抑制剂被用作治疗这种疾病的相关药物,以提高乙酰胆碱的水平。另一方面,研究发现,高水平的乙酰胆碱与临床抑郁症的症状有关。

本文旨在探讨作为抗阿尔茨海默病药物使用的乙酰胆碱酯酶抑制剂是否可能是这种神经障碍常伴有的临床抑郁症症状的原因。重点将放在目前正在使用的药物和新研究的天然产物上,这些药物可以抑制乙酰胆碱酯酶的活性。

目前,由于乙酰胆碱酯酶抑制,接受阿尔茨海默病治疗的患者是否更容易患上抑郁症的风险,还没有得到证实,但有强烈的迹象表明。在像 AD 和抑郁症这样高度复杂的疾病中,乙酰胆碱的水平并不是唯一的因素。尽管如此,在进行合理的药物设计过程时,需要单独考虑这个因素,同时要牢记目前可用的治疗方法的性质。

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