PubMed1999
AIM: To study the neuroprotective, neurorescue, neurorestorative effects of selegiline (Sel) on nigrostriatal dopaminergic neuronal system and its inhibition of brain monoamine oxidase B (MAO-B). METHODS: The striatal levels of dopamine and its metabolites were measured using HPLC with electrochemical detection (HPLC-EC). The inhibition of MAO-B was tested by an improved fluorimetric assay. RESULTS: 1-Methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) (30 mg.kg-1 i.p.) reduced the striatal dopamine level by 73% in mice. Selegiline (Sel, 10 mg.kg-1 i.p.) before, but not after, MPTP treatment protected against MPTP-induced nigrostriatal dopaminergic neurotoxicity. There were no differential effects between Sel and saline treatments on the recovery of striatal dopamine levels, which were partially restored during 2 wk. 1-Methyl-4-phenylpyridinium (MPP+) (5 mg.kg-1 i.p.) produced no dopaminergic neurotoxicity. Furthermore, Sel selectively and irreversibly inhibited mouse brain MAO-B in vitro (IC50 = 17 nmol.L-1, 95% confidence limits = 14-20 nmol.L-1). CONCLUSION: Selegiline has neuroprotective rather than neurorescue or neurorestorative effects on MPTP-induced nigrostriatal dopaminergic neuronal degeneration, which is directly pertinent to its selective and irreversible inhibition of brain MAO-B activity.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗