1. ^aDepartment of Clinical Neurochemistry, University of Würzburg, Würzburg
2. ^bDepartment of Pharmacology, Faculty of Medicine, Technion, Haifa

^* The drug names d- and l-methamphetamine used in this article have been commonly employed in the experimental literature and are used herein. It should be noted, however, that methamphetamine does not exist in racemic form but d-methamphetamine instead refers to the d-isomer of N-methylamphetamine and that l-methamphetamine is more correctly named l-N-methylamphetamine.

Abstract

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.