Effects of R- and S-apomorphine on MPTP-induced nigro-striatal dopamine neuronal loss

In order to establish whether the antioxidant and iron-chelating activities of R-apomorphine (R-APO), a D-1-D-2 receptor agonist, may contribute to it s neuroprotective property, its S-isomer, which is not a dopamine agonist, was studied. The neuroprotective property of R- and S-APO has been studied in the MPTP model of Parkinson's disease (PD). Both S-APO (0.5-1 mg/kg, sub cutaneous) and R-APO (10 mg/kg) pretreatment of C57-BL mice, protected agai nst MPTP (24 mg/kg, intraperitoneally) induced dopamine (DA) depletion and reduction in tyrosine hydroxylase (TH) activity. However, only R-APO preven ted nigro-striatal neuronal cell degeneration, as indicated by the immunohi stochemistry of TH positive neurones in substantia nigra and by western ana lysis of striatal TH content. R-APO prevented the reduction of striatal-GSH and the increase in the ratio of GSSG over total glutathione, caused by MP TP treatment. In vitro both R-APO and S-APO inhibited monoamine oxidase A a nd B activity at relatively high concentrations (100 and 300 mu mol/L, resp ectively). The elevated activity of TH induced by the two enantiomers may c ontribute to the maintenance of normal DA levels, suggesting that one of th e targets of these molecules may involve upregulation of TH activity. It is suggested that the antioxidant and iron-chelating properties, possible mon oamine oxidase inhibitory actions, together with activation of DA receptors , may participate in the mechanism of neuroprotection by APO enantiomers ag ainst MPTP.