Fišar Zdeněk
Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic.
Prog Neuropsychopharmacol Biol Psychiatry. 2016 Aug 1;69:112-24. doi: 10.1016/j.pnpbp.2016.02.012. Epub 2016 Mar 2.
Progress in understanding the role of monoamine neurotransmission in pathophysiology of neuropsychiatric disorders was made after the discovery of the mechanisms of action of psychoactive drugs, including monoamine oxidase (MAO) inhibitors. The increase in monoamine neurotransmitter availability, decrease in hydrogen peroxide production, and neuroprotective effects evoked by MAO inhibitors represent an important approach in the development of new drugs for the treatment of mental disorders and neurodegenerative diseases. New drugs are synthesized by acting as multitarget-directed ligands, with MAO, acetylcholinesterase, and iron chelation as targets. Basic information is summarized in this paper about the drug-induced regulation of monoaminergic systems in the brain, with a focus on MAO inhibition. Desirable effects of MAO inhibition include increased availability of monoamine neurotransmitters, decreased oxidative stress, decreased formation of neurotoxins, induction of pro-survival genes and antiapoptotic factors, and improved mitochondrial functions.
在发现包括单胺氧化酶(MAO)抑制剂在内的精神活性药物的作用机制后,人们对单胺神经传递在神经精神疾病病理生理学中的作用有了进一步认识。MAO抑制剂引起的单胺神经递质可用性增加、过氧化氢生成减少以及神经保护作用,是开发治疗精神障碍和神经退行性疾病新药的重要途径。通过作为多靶点导向配体合成新药,以MAO、乙酰胆碱酯酶和铁螯合为靶点。本文总结了关于药物诱导大脑单胺能系统调节的基本信息,重点是MAO抑制。MAO抑制的理想效果包括单胺神经递质可用性增加、氧化应激降低、神经毒素形成减少、促生存基因和抗凋亡因子的诱导以及线粒体功能改善。