L-deprenyl protects mesencephalic dopamine neurons from glutamate receptor-mediated toxicity in vitro.
L-Deprenyl is a relatively selective inhibitor of monoamine oxidase (MAO)-B that delays the emergence of disability and the progression of signs and symptoms of Parkinson's disease. Experimentally, deprenyl has also been shown to prevent neuronal cell death in various models through a mechanism that is independent of MAO-B inhibition. We examined the effect of deprenyl on cultured mesencephalic dopamine neurons subjected to daily changes of feeding medium, an experimental paradigm that causes neuronal death associated with activation of the NMDA subtype of glutamate receptors. Both deprenyl (0.5-50 microM) and the NMDA receptor blocker MK-801 (10 microM) protected dopamine neurons from damage caused by medium changes. The nonselective MAO inhibitor pargyline (0.5-50 microM) was not protective, indicating that protection by deprenyl was not due to MAO inhibition. Deprenyl (50 microM) also protected dopamine neurons from delayed neurotoxicity caused by exposure to NMDA. Because deprenyl had no inhibitory effect on NMDA receptor binding, it is likely that deprenyl protects from events occurring downstream from activation of glutamate receptors. As excitotoxic injury has been implicated in neurodegeneration, it is possible that deprenyl exerts its beneficial effects in Parkinson's disease by suppressing excitotoxic damage.
Mytilineou
C
C
Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Radcliffe
P
P
Leonardi
E K
EK
Werner
P
P
Olanow
C W
CW
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats / Q000196:embryology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D012642:Selegiline / Q000494:pharmacology*
D003470:Culture Media; D018691:Excitatory Amino Acid Antagonists; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D017470:Receptors, Glutamate; C069052:CGP 39653; D012642:Selegiline; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D010293:Pargyline; D004298:Dopamine