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.