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单胺氧化酶抑制型抗抑郁药苯乙肼的神经保护作用概述。

Overview of the Neuroprotective Effects of the MAO-Inhibiting Antidepressant Phenelzine.

作者信息

Matveychuk Dmitriy, MacKenzie Erin M, Kumpula David, Song Mee-Sook, Holt Andrew, Kar Satyabrata, Todd Kathryn G, Wood Paul L, Baker Glen B

机构信息

Department of Psychiatry (Neurochemical Research Unit), University of Alberta, 12-105B Clinical Sciences Building, Edmonton, AB, T6G 2G3, Canada.

Altos Biologics, Seoul, South Korea.

出版信息

Cell Mol Neurobiol. 2022 Jan;42(1):225-242. doi: 10.1007/s10571-021-01078-3. Epub 2021 Apr 10.

DOI:10.1007/s10571-021-01078-3
PMID:33839994
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8732914/
Abstract

Phenelzine (PLZ) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic properties. This multifaceted drug has a number of pharmacological and neurochemical effects in addition to inhibition of MAO, and findings on these effects have contributed to a body of evidence indicating that PLZ also has neuroprotective/neurorescue properties. These attributes are reviewed in this paper and include catabolism to the active metabolite β-phenylethylidenehydrazine (PEH) and effects of PLZ and PEH on the GABA-glutamate balance in brain, sequestration of reactive aldehydes, and inhibition of primary amine oxidase. Also discussed are the encouraging findings of the effects of PLZ in animal models of stroke, spinal cord injury, traumatic brain injury, and multiple sclerosis, as well other actions such as reduction of nitrative stress, reduction of the effects of a toxin on dopaminergic neurons, potential anticonvulsant actions, and effects on brain-derived neurotrophic factor, neural cell adhesion molecules, an anti-apoptotic factor, and brain levels of ornithine and N-acetylamino acids.

摘要

苯乙肼（PLZ）是一种具有抗焦虑特性的单胺氧化酶（MAO）抑制型抗抑郁药。除抑制MAO外，这种多方面作用的药物还具有许多药理和神经化学作用，关于这些作用的研究结果促成了一系列证据，表明PLZ还具有神经保护/神经挽救特性。本文对这些特性进行了综述，包括代谢为活性代谢物β-苯乙叉肼（PEH）以及PLZ和PEH对大脑中γ-氨基丁酸-谷氨酸平衡的影响、捕获反应性醛以及抑制伯胺氧化酶。还讨论了PLZ在中风、脊髓损伤、创伤性脑损伤和多发性硬化症动物模型中的作用的令人鼓舞的研究结果，以及其他作用，如降低硝化应激、减轻毒素对多巴胺能神经元的影响、潜在的抗惊厥作用，以及对脑源性神经营养因子、神经细胞粘附分子、一种抗凋亡因子以及大脑中鸟氨酸和N-乙酰氨基酸水平的影响。

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