Monoamine oxidase activity and monoamine metabolism in brains of parkinsonian patients treated with l-deprenyl

J Neurochem. 1986 May;46(5):1359-65. doi: 10.1111/j.1471-4159.1986.tb01747.x.

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).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amines / metabolism*
  • Brain / enzymology*
  • Dopamine / metabolism
  • Female
  • Humans
  • Hydroxyindoleacetic Acid / metabolism
  • Indans / pharmacology
  • Kynuramine / metabolism
  • Male
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / pharmacology
  • Parkinson Disease / drug therapy
  • Parkinson Disease / enzymology*
  • Phenethylamines / therapeutic use*
  • Selegiline / pharmacology
  • Selegiline / therapeutic use*
  • Serotonin / metabolism
  • Tissue Distribution
  • Tranylcypromine / pharmacology

Substances

  • Amines
  • Indans
  • Monoamine Oxidase Inhibitors
  • Phenethylamines
  • rasagiline
  • Selegiline
  • Serotonin
  • Kynuramine
  • Tranylcypromine
  • Hydroxyindoleacetic Acid
  • Monoamine Oxidase
  • Dopamine