Localization of MAO-A and MAO-B in human brain: a step in understanding the therapeutic action of L-deprenyl.
The discovery that MAO can be differentiated biochemically and pharmacologically into two forms, types A and B, with different substrate specificities and inhibitor sensitivities has renewed the interest in MAO inhibiting as a therapeutic agent. L-Deprenyl, a selective inhibitor of MAO-B, was introduced by us into clinical use as an adjunct to L-DOPA some years ago. This drug has found therapeutic importance in that it can potentiate the pharmacological action of L-DOPA. The mechanism underlying the action of L-deprenyl is thought to be related to its inhibition of MAO-B and thus increased levels of PEA and DA, as measured in the striatal and limbic region of human brain. Animal studies have indicated the MAO-A is mainly, but not exclusively, located in brain neurons, while MAO-B is preferentially placed in glia and astrocytes. In general human and primate brain studies show similar MAO distribution. The observation that MAO-B activity could not be located in the catecholaminergic neurons of human brain by the use of monoclonal antibody studies seriously questions the validity of this technique. The exact locations of MAO-A and -B in human brain are important to understand the mechanism of L-deprenyl action as an antiparkinson drug. If there is an absence of MAO-B from dopaminergic neurons, one may now consider that MAO-B activity within glia plays a far more important role than hitherto considered. This, however, is questionable.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D004298:Dopamine / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008252:Macaca fascicularis; D008995:Monoamine Oxidase / Q000378:metabolism*; D009457:Neuroglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D009638:Norepinephrine / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology*; D010627:Phenethylamines / Q000627:therapeutic use*; D012642:Selegiline / Q000627:therapeutic use*; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D007527:Isoenzymes; D010627:Phenethylamines; D012642:Selegiline; D012701:Serotonin; D008995:Monoamine Oxidase; D004298:Dopamine; D009638:Norepinephrine