Biochemical actions of l-deprenyl (selegiline).
l-Deprenyl is a selective, irreversible monoamine oxidase (MAO) type B inhibitor. Dopamine is a relatively good MAO-B substrate in the human brain. Because Parkinson's disease is characterized by a decrease in dopaminergic neurotransmission in the basal ganglia, the selective inhibition of MAO-B should lead to diminished metabolism of dopamine in the nigrostriatal system and a significant increase in the concentration of the neurotransmitter. MAO-B inhibition explains the clinical efficacy of l-deprenyl in the treatment of Parkinson's disease and the prevention of the conversion of protoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which is oxidized by MAO-B and can cause a parkinsonian syndrome, to their active neurotoxin. In addition, l-deprenyl appears to exhibit other biochemical actions that are independent of its MAO-B activity. These actions may be the basis of the neuroprotective effects of l-deprenyl and may include the inhibition of oxidative stress, an indirect influence on the polyamine binding site of the N-methyl-d-aspartate receptor and the stimulation of neurotrophic factors.
Lange
K W
KW
Department of Clinical Neurochemistry, University of Würzburg.
Riederer
P
P
Youdim
M B
MB
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012642:Selegiline / Q000737:chemistry / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000096:biosynthesis
D016194:Receptors, N-Methyl-D-Aspartate; D012642:Selegiline; D013482:Superoxide Dismutase