Wr. Wu et al., Neuroprotective rather than neurorescue or neurorestorative effect of selegiline against MPTP-induced dopaminergic toxicity, ACT PHAR SI, 20(2), 1999, pp. 146-150
AIM: To study the neuroprotective, neurorescue, neurorestorative effects of
selegiline (Sel) on nigrostriatal dopaminergic neuronal system and its inh
ibition of brain monoamine oxidase B (MAO-B). METHODS: The striatal levels
of dopamine and its metabolites were measure using HPLC with electrochemica
l detection (HPLC-EC). The inhibition of MAO-B was tested by an improved fl
uorimetric assay. RESULTS: 1-Methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (M
PTP) (30 mg . kg(-1) ip) reduced the striatal dopamine level by 73% in mice
. Selegiline (Sel, 10 mg . kg(-1) ip) before, but not after, MPTP treatment
protected against MPTP-induced nigrostriatal dopaminergic neurotoxicity. T
here 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) ip) produced no do
paminergic neurotoxicity. Furthermore, Sel selectively and irreversibly inh
ibited mouse brain MAO-B in vitro (IC50 = 17 nmol.L-1, 95% confidence limit
s = 14 - 20 nmol.L-1). CONCLUSION: Selegiline has neuroprotective rather th
an neurorescue or neurorestorative effects on MPTP-induced nigrostriatal do
paminergic neuronal degeneration, which is directly pertinent to its select
ive and irreversible inhibition of brain MAO-B activity.