l‐(−)‐Desmethylselegiline, a Metabolite of Selegiline [l‐(−)‐Deprenyl], Protects Mesencephalic Dopamine Neurons from Excitotoxicity In Vitro

• Published in: Journal of neurochemistry Vol. 68; no. 1; pp. 434 - 436
• Main Authors: Mytilineou, Catherine, Radcliffe, Pheona M., Olanow, C. Warren
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.1997; Blackwell
• Subjects: Amphetamines - metabolism; Amphetamines - pharmacology; Animals; Biological and medical sciences; Cell Survival - drug effects; Cells, Cultured; Desmethylselegiline; Dopamine - physiology; Excitotoxicity; l‐Deprenyl; Medical sciences; Mesencephalon - cytology; Mesencephalon - drug effects; Mesencephalon - physiology; Monoamine Oxidase Inhibitors - pharmacology; Neurons - drug effects; Neurons - physiology; Neuropharmacology; Neuroprotection; Neuroprotective agent; Neuroprotective Agents - pharmacology; Neurotoxins - pharmacology; Parkinson's disease; Pharmacology. Drug treatments; Rats - embryology; Selegiline; Selegiline; Rat; Metabolite; Toxicity; Rodentia; Parkinson disease; Glutamate receptor; Neuroprotective agent; Vertebrata; Mammalia; Animal; Dopaminergic neuron; NMDA receptor; Brain (vertebrata)
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1997.68010434.x

: Selegiline [l‐(−)‐deprenyl], a monoamine oxidase B inhibitor, has been used in the treatment of Parkinson's disease as a putative neuroprotective agent. Selegiline is metabolized rapidly in the gastrointestinal tract and liver to desmethylselegiline (DMS) and methamphetamine. We have previously shown that selegiline protects dopamine neurons in mesencephalic cultures from toxicity resulting from activation of glutamate receptors. In the present study we examined whether DMS has similar neuroprotective effects. Our data show that DMS protects dopamine neurons from N‐methyl‐d‐aspartate receptor‐mediated excitotoxic damage. The efficacy of DMS is greater than that of selegiline, as it can cause protection at lower concentrations and provide significantly greater levels of protection at the same concentrations. Our results suggest that DMS might be the active compound responsible for the neuroprotective properties of selegiline.