Monoamine Oxidase Activity and Monoamine Metabolism in Brains of Parkinsonian Patients Treated with <i>l</i>‐Deprenyl

Abstract

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).