Neuroprotection by (R)-deprenyl and 7-nitroindazole in the MPTP C57BL/6 mouse model of neurotoxicity.
The neurodegenerative properties of the parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are thought to result from inhibition of complex I of the mitochondrial respiratory chain by the monoamine oxidase-B (MAO-B) generated 1-methyl-4-phenylpyridinium metabolite MPP+. 7-Nitroindazole (7-NI) both a reversible MAO-B inhibitor and a neuronal nitric oxide synthase (nNOS) inhibitor, and (R)-deprenyl a potent MAO-B inactivator, provide neuroprotection in the C57BL/6 mouse model of MPTP neurotoxicity. The results reported here demonstrate the complexities of the effects of 7-NI in this model and examine the possibility of other mechanisms of neuroprotection by (R)-deprenyl.
Castagnoli
K
K
Department of Chemistry, Harvey W. Peters Center, Virginia Tech, Blacksburg 24061-0212, USA.
Palmer
S
S
Castagnoli
N
N
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism / Q000494:pharmacology*; D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002417:Cattle; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology*
D007191:Indazoles; D018696:Neuroprotective Agents; D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; D015655:1-Methyl-4-phenylpyridinium; C080122:7-nitroindazole; D004298:Dopamine