Protection against MPTP treatment by an analog of Pro-Leu-Gly-NH2 (PLG, MIF-1)
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.
Marcotte
E R
ER
Department of Psychiatry, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Chugh
A
A
Mishra
R K
RK
Johnson
R L
RL
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D020267:MPTP Poisoning; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000378:metabolism / Q000517:prevention & control; D011760:Pyrrolidinones / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects
D006727:Hormone Antagonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011760:Pyrrolidinones; D011954:Receptors, Dopamine; C067487:3-(N-prolylamine)-2-oxo-1-pyrrolidineacetamide; D009075:MSH Release-Inhibiting Hormone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine