Deprenyl rescues dopaminergic neurons in organotypic slice cultures of neonatal rat mesencephalon from N-methyl-D-aspartate toxicity.

The potential neuroprotective effect of (-)-deprenyl (R-N,alpha-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 microM) 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 H2O2. 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.