Abstract

The potential neuroprotective effect of (−)-deprenyl ( R- N,α-dimethyl- N-2-propynylbenzeneethanamine) against N-methyl- d-aspartate (NMDA) excitotoxicity was investigated on rat mesencephalic dopaminergic neurons in organotypic slice cultures. While 24 h application of NMDA (100 μM) caused a marked decrease in the number of surviving dopaminergic neurons, simultaneous application of (−)-deprenyl significantly attenuated the cytotoxic effect of NMDA. (+)-Deprenyl showed a less potent but still significant protective effect against NMDA insult. Pre-treatment of cultures with (−)-deprenyl conferred no protection against subsequent NMDA insult, suggesting that the protective effect of (−)-deprenyl may be independent of its irreversible inhibitory action on monoamine oxidase B. (−)-Deprenyl was also ineffective in preventing cell death induced by H 2O 2. These results indicated that (−)-deprenyl protects dopaminergic neurons from NMDA excitotoxicity through a mechanism distinct from monoamine oxidase inhibition or detoxification of reaction oxygen species.

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