Potent neuroprotective and antioxidant activity of apomorphine in MPTP and 6-hydroxydopamine induced neurotoxicity.
Apomorphine is a potent radical scavenger and iron chelator. In vitro apomorphine acts as a potent iron chelator and radical scavenger with IC50 of 0.3 microM for iron (2.5 microM) induced lipid peroxidation in rat brain mitochondrial preparation, and it inhibits mice striatal MAO-A and MAO-B activities with IC50 values of 93 microM and 241 microM. Apomorphine (1-10 microM) protects rat pheochromocytoma (PC12) cells from 6-hydroxydopamine (150 microM) and H2O2 (0.6 mM) induced cytotoxicity and cell death. 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. (R)-apomorphine (5-10 mg/kg, s.c.) pretreatment in C57BL mice, protects against MPTP (24 mg/kg, i.p.) induced loss of nigro-striatal dopamine neurons, as indicated by striatal dopamine content, tyrosine hydroxylase content and tyrosine hydroxylase activity. 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, since the mechanism of MPTP dopaminergic neurotoxicity involves the generation of oxygen radical species induced-oxidative stress.
Grünblatt
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E
Technion-Faculty of Medicine, Eve Topf, Haifa, Israel.
Mandel
S
S
Gassen
M
M
Youdim
M B
MB
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology; D020267:MPTP Poisoning; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats
D000975:Antioxidants; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016627:Oxidopamine; D001058:Apomorphine