Apomorphine protects against MPTP-induced neurotoxicity in mice.
R-apomorphine is a potent radical scavenger and iron chelator. The neuroprotective property of R-apomorphine, a dopamine D1-D2 receptor agonist, has been studied in the MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease. Pretreatment with 5-10 mg/kg R-apomorphine administered subcutaneously in C57BL mice protects against MPTP (24 mg/kg administered intraperitoneally) induced loss of nigrostriatal dopamine neurons as indicated by striatal dopamine content, tyrosine hydroxylase content, and tyrosine hydroxylase activity. In vitro, R-apomorphine inhibited mice striatal MAO-A and MAO-B activities with IC50 values of 93 microM and 241 microM. It is suggested that the neuroprotective effect of R-apomorphine against MPTP neurotoxicity derives from its radical scavenging and MAO inhibitory actions and not from its agonistic activity because the mechanism of MPTP dopaminergic neurotoxicity involves the generation of oxygen radical species-induced oxidative stress.
Grünblatt
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Technion Faculty of Medicine, Eve Topf and US National Parkinson's Foundation Centers for Neurodegenerative Diseases, Bruce Rappaport Family Research Institute, Haifa, Israel.
Mandel
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Berkuzki
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T
Youdim
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MB
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010300:Parkinson Disease / Q000209:etiology / Q000517:prevention & control*; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; D001058:Apomorphine; D004298:Dopamine