Abstract
3(R)-[(2(S)-Pyrrolidinyl-carbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) is a peptidomimetic analog of Pro-Leu-Gly-NH2 (PLG or MIF-1) that has previously been demonstrated to be more potent and efficacious that MIF-1 in enhancing dopamine receptor activity. Given the ability of MIF-1 to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioning in C57 BL/6 mice, the present study was undertaken to evaluate the neuroprotective effect of PAOPA in this model. PAOPA was found to be more potent and efficacious that MIF-1 in sparing dopamine and its metabolite levels following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Whether the enhanced neuroprotective effect of PAOPA is due to dopamine receptor stimulation, or a result of reduced oxidative stress through normalization of dopamine turnover, remains to be determined.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / antagonists & inhibitors*
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Animals
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Corpus Striatum / drug effects
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Corpus Striatum / metabolism
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Disease Models, Animal
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Dopamine / metabolism
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Hormone Antagonists / pharmacology
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MPTP Poisoning
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MSH Release-Inhibiting Hormone / analogs & derivatives*
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MSH Release-Inhibiting Hormone / pharmacology
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Male
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Mice
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Mice, Inbred C57BL
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Nerve Degeneration / prevention & control
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Neuroprotective Agents / pharmacology
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Neurotoxins / antagonists & inhibitors
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Neurotoxins / toxicity
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Parkinson Disease, Secondary / metabolism
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Parkinson Disease, Secondary / prevention & control
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Pyrrolidinones / pharmacology*
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Receptors, Dopamine / drug effects
Substances
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Hormone Antagonists
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Neuroprotective Agents
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Neurotoxins
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Pyrrolidinones
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Receptors, Dopamine
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3-(N-prolylamine)-2-oxo-1-pyrrolidineacetamide
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MSH Release-Inhibiting Hormone
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Dopamine