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新一代的单胺氧化酶抑制剂

[Inhibitory monoamine oxidases of the new generation].

作者信息

Nowakowska E, Chodera A

机构信息

Zakładu Farmakologii Akademii Medycznej w Poznaniu.

出版信息

Pol Merkur Lekarski. 1997 Jul;3(13):1-4.

PMID:9432289
Abstract

This review deals with the new generation of selective and partly reversible monoamine oxidase (MAO) inhibitors. In contrast to the non selective inhibitors, used in the year 1957-1970, the selective inhibitors bind to and block only one of the two isoenzymes, MAO-A or MAO-B. The MAO-A inhibitors and part of the MAO-B inhibitors differ also from the classic drugs by their reversibility. The inhibition of MAO-A cause the rise of norepinephrine, dopamine and serotonin in the synaptic cleft, of MAO-B only of dopamine. The new inhibitors diminish also to some extent the reuptake of monoamines. The molecular action mechanism of the new drug generation is the same as in the non-selective drugs: increase of monoamines, near to the receptor, leads, after a number of intermediate steps, to activation of functional proteins in the cell. The selective block of one of the isoenzymes does not stop the metabolism of tyramine (from cheese, red wine), because this toxic compound is metabolised by both isoenzymes. The control of therapy with MAO-A inhibitors is easier, because of their reversibility. Selective inhibitors of MAO have found a secure place in therapy of depression (inh. of MAO-A, esp. Moclobemide) and Parkinson's disease (inh. of MAO-B, at this time mainly selegiline). Discussed is possible use of selective MAO-inhibitors for achieving an increase in cognitive function and protections of neurone cells from biochemical lesions.

摘要

本综述涉及新一代选择性且部分可逆的单胺氧化酶(MAO)抑制剂。与1957年至1970年使用的非选择性抑制剂不同,选择性抑制剂仅与两种同工酶之一(MAO - A或MAO - B)结合并阻断其活性。MAO - A抑制剂以及部分MAO - B抑制剂在可逆性方面也与传统药物不同。抑制MAO - A会导致突触间隙中去甲肾上腺素、多巴胺和5-羟色胺水平升高,而抑制MAO - B仅会使多巴胺水平升高。新型抑制剂在一定程度上还会减少单胺的再摄取。新一代药物的分子作用机制与非选择性药物相同:靠近受体的单胺增加,经过一系列中间步骤后,会导致细胞内功能蛋白的激活。对其中一种同工酶的选择性阻断并不会阻止酪胺(来自奶酪、红酒)的代谢,因为这种有毒化合物可由两种同工酶代谢。由于MAO - A抑制剂具有可逆性,其治疗控制相对更容易。MAO选择性抑制剂在抑郁症治疗(MAO - A抑制剂,尤其是吗氯贝胺)和帕金森病治疗(MAO - B抑制剂,目前主要是司来吉兰)中已占据了稳固的地位。文中还讨论了选择性MAO抑制剂在提高认知功能以及保护神经元细胞免受生化损伤方面的可能用途。

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