Potent neuroprotective and antioxidant activity of apomorphine in MPTP and6-hydroxydopamine induced neurotoxicity

Apomorphine is a potent radical scavenger and iron chelator. In vitro apomo rphine acts as a potent iron chelator and radical scavenger with IC50 of 0. 3 mu M for iron (2.5 mu M) induced lipid peroxidation in rat brain mitochon drial preparation, and it inhibits mice striatal MAO-A and MAO-B activities with IC50 values of 93 mu M and 241 mu M. Apomorphine (1-10 mu M) protects rat pheochromocytoma (PC12) cells from 6-hydroxydopamine (150 mu M) and H2 O2 (0.6mM) induced cytotoxicity and cell death. The neuroprotective propert y of (R)-apomorphine, a dopamine D-1-D-2 receptor agonist, has been studied in the MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkin son's disease. (R)-apomorphine (5-10 mg/kg, s.c.) pretreatment in C57BL mic e, protects against MPTP (24 mg/kg, I.P) induced loss of nigro-striatal dop amine neurons, as indicated by striatal dopamine content, tyrosine hydroxyl ase content and tyrosine hydroxylase activity. It is suggested that the neu roprotective effect of (R)-apomorphine against MPTP neurotoxicity derives f rom its radical scavenging and MAO inhibitory actions and not from its agon istic activity, since the mechanism of MPTP dopaminergic neurotoxicity invo lves the generation of oxygen radical species induced-oxidative stress.