Iron chelating, antioxidant and cytoprotective properties of dopamine receptor agonist; apomorphine.
There have been many attempts to discover neuroprotective drugs for the treatment of Parkinson's disease (PD). Many of these compounds either do not cross the blood brain barrier or are not very effective in the 6-hydroxydopamine or MPTP (N-methyl-4-phenyl-1,2,3,6-terahydropyridine) models of PD. We have examined several compounds including dopamine receptor agonist bromocritine, lisuride, pergolide and R-apomorphine for their neuroprotective action against the above neurotoxins in PC12 and dopamine neuroblastoma cell lines in culture and in vivo. R-apomorphine exhibited relatively potent neuroprotective action in vitro, cell culture and in vivo as a radical scavenger and iron chelator, because of its catechol structure. The recent clinical trials with apomorphine, where parkinsonian subjects can be weaned off L-dopa would suggest that this drug either exerts a neuroprotective action or that continuous sustained stimulation of dopamine receptor may be responsible for its unusual pharmacological activity. Apomorphine has a far more broad neuroprotective activity in the various models as compared with 1-selegiline and may therefore be an ideal drug to study neuroprotection in parkinsonian subjects with the use of PET or SPECT.
Youdim
M B
MB
Department of Pharmacology, Eve Topf and National Parkinson's Foundation Centers, Bruce Rappaport Family Research Institute, Faculty of Medicine, Technion, Haifa, Israel. youdim@tx.technion.ac.il
Gassen
M
M
Gross
A
A
Mandel
S
S
Grünblatt
E
E
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D006801:Humans; D007501:Iron; D010300:Parkinson Disease / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D002614:Chelating Agents; D018491:Dopamine Agonists; D017382:Reactive Oxygen Species; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D007501:Iron; D001058:Apomorphine