The relevance of glial monoamine oxidase-B and polyamines to the action of selegiline in Parkinson's disease.
Dopamine and 2-phenylethylamine levels in striatal tissue are known to be increased after administration of selegiline (L-deprenyl), but it is still difficult to explain why this treatment induces longevity or dopaminergic neuroprotection in Parkinson's disease. In the absence of significant polyamine or diamine oxidase activities in human brain, polyamines and histamine are detoxified by N-acetylation and methylation, respectively. Methylhistamine as well as N-acetylated polyamine derivatives are selective substrates for monoamine oxidase type B (MAO-B). Theoretically at least, MAO-B inhibition by selegiline could result in the increase in the levels of polyamines and their N-acetyl derivatives. This could have significance for the action of selegiline in Parkinson's disease, as overactive corticostriatal glutaminergic function has been implicated in the degeneration of nigrostriatal dopamine neurons, and polyamines are potent modulators of the excitotoxic NMDA (N-methyl-D-aspartate)-glutamate subtype receptor.
Youdim
M B
MB
Department of Pharmacology, Technion, Haifa, Israel.
Riederer
P
P
D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D008995:Monoamine Oxidase / Q000502:physiology*; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D009410:Nerve Degeneration / Q000187:drug effects / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects* / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D011073:Polyamines / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012642:Selegiline / Q000627:therapeutic use*; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology
D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D011073:Polyamines; D017382:Reactive Oxygen Species; D012642:Selegiline; D008995:Monoamine Oxidase; D004298:Dopamine