PROTECTION AGAINST MPTP TREATMENT BY AN ANALOG OF PRO-LEU-GLY-NH2 (PLG, MIF-1)

idinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) is a peptid omimetic analog of Pro-Leu-Gly-NH2 (PLG or MLF-1) that has previously been demonstrated to be more potent and efficacious that MLF-1 in enha ncing dopamine receptor activity. Given the ability of MIF-1 to protec t against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesionin g in C57 BL/6 mice, the present study was undertaken to evaluate the n europrotective effect of PAOPA in this model. PAOPA was found to be mo re potent and efficacious that MIF-1 in sparing dopamine and its metab olite levels following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ad ministration. 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 dete rmined. (C) 1998 Elsevier Science Inc.