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 nigostriatal 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.