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.
Shimazu
S
S
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Katsuki
H
H
Akaike
A
A
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D046508:Culture Techniques; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007150:Immunohistochemistry; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016877:Oxidants; D012642:Selegiline; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D006861:Hydrogen Peroxide; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine