Abstract

Parkinsonism (PD) is a neurodegenerative disorder of the brain resulting in dopamine deficiency caused by the progressive death of dopaminergic neurons. PD is characterized by a combination of rigidity, poverty of movement, tremor and postural instability. Selegiline is a selective and irreversible propargylamine type B monoamine oxidase (MAO‐B) inhibitor. This drug, which inhibits dopamine metabolism, has been effectively used in the treatment of PD. However, its therapeutic effects are compromised by its many neurotoxic metabolites. To circumvent this obstacle, a novel MAO‐B inhibitor, rasagiline, was developed. Paradoxically, the neuroprotective mechanism of propargylamines in different neuronal models appears to be independent of MAO‐B inhibition. Recent investigations into the neuroprotective mechanism of propargylamines indicate that glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), MAO‐B and/or other unknown proteins may represent pivotal proteins in the survival of the injured neurons. Delineation of the mechanism(s) involved in the neuroprotective effects exerted by MAO‐B inhibitors may provide the key to preventive novel therapeutic modalities. BioEssays 26:80–90, 2004. © 2003 Wiley Periodicals, Inc.