Premium
l ‐(−)‐Desmethylselegiline, a Metabolite of Selegiline [ l ‐(−)‐Deprenyl], Protects Mesencephalic Dopamine Neurons from Excitotoxicity In Vitro
Author(s) -
Mytilineou Catherine,
Radcliffe Pheona M.,
Olanow C. Warren
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68010434.x
Subject(s) - selegiline , neuroprotection , excitotoxicity , pharmacology , dopamine , metabolite , chemistry , monoamine oxidase b , glutamate receptor , monoamine oxidase , receptor , biochemistry , medicine , parkinson's disease , enzyme , disease
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.