Riederer P, Youdim M B
J Neurochem. 1986 May;46(5):1359-65. doi: 10.1111/j.1471-4159.1986.tb01747.x.
Monoamine oxidase (MAO) type A and type B were measured using kynuramine, 3,4-dihydroxyphenylethylamine (dopamine, DA), and 5-hydroxytryptamine (5-HT, serotonin) in 20 brain areas. The highest activities were found in the striatum (caudate nucleus, putamen, globus pallidus, and substantia nigra), hypothalamus, and c-mammilare. The ratio of DA to 5-HT deamination varied in the different regions, being in favor of DA in the striatum. With kynuramine as the substrate IC50 values of a number of inhibitors indicated that l-deprenyl was far more potent an inhibitor of human brain MAO than clorgyline or harmaline. N-Desmethylpropargylindane hydrochloride (AGN 1135) was also shown to have MAO-B inhibitory selectivity similar to that of l-deprenyl. Brains obtained at autopsy from l-deprenyl-treated Parkinsonian patients showed that, whereas MAO-B was fully inhibited by the therapeutic doses of l-deprenyl, substantial MAO-A activity was still evident. These results are matched by the significant increases of DA noted in caudate nucleus, globus pallidus, putamen, and substantia nigra and the unaltered 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the same regions. These data indicate that the therapeutic actions of l-deprenyl may lie in its selective inhibition of MAO-B resulting in increased brain levels of DA formed from L-dihydroxyphenylacetic acid (L-DOPA).
使用犬尿胺、3,4-二羟基苯乙胺（多巴胺，DA）和5-羟色胺（5-HT，血清素）测定了20个脑区的A型和B型单胺氧化酶（MAO）。在纹状体（尾状核、壳核、苍白球和黑质）、下丘脑和乳头体中发现了最高活性。不同区域DA与5-HT脱氨基的比例各不相同，在纹状体中有利于DA。以犬尿胺为底物，多种抑制剂的IC50值表明，左旋丙炔苯丙胺作为人脑MAO的抑制剂比氯吉兰或哈马灵更有效。盐酸N-去甲基炔丙基茚满（AGN 1135）也显示出与左旋丙炔苯丙胺相似的MAO-B抑制选择性。从接受左旋丙炔苯丙胺治疗的帕金森病患者尸检获得的大脑显示，虽然治疗剂量的左旋丙炔苯丙胺可完全抑制MAO-B，但仍有明显的MAO-A活性。这些结果与尾状核、苍白球、壳核和黑质中DA的显著增加以及同一区域中5-HT和5-羟吲哚乙酸（5-HIAA）未改变相匹配。这些数据表明，左旋丙炔苯丙胺的治疗作用可能在于其对MAO-B的选择性抑制，从而导致由L-二羟基苯乙酸（L-DOPA）形成的大脑DA水平升高。
