APOMORPHINE ENANTIOMERS PROTECT CULTURED PHEOCHROMOCYTOMA (PC12) CELLS FROM OXIDATIVE STRESS-INDUCED BY H2O2 AND 6-HYDROXYDOPAMINE

A significant body of evidence has been provided to support the hypoth esis that oxidant stress may be responsible for the degeneration of do paminergic neurons in the substantia nigra pars compacta in Parkinson' s disease. Apomorphine, a dopamine D-1/D-2-receptor agonist in the cli nical therapy of Parkinson's disease, has been found to be a potent an tioxidant and to prevent free radical reaction in rat brain mitochondr ial fraction. In this article we show that 1-10 mu M of apomorphine pr otects rat pheochromocytoma (PC12) cells from the toxic effects of H2O 2 (0.6 mM) and the neurotoxin 6-hydroxydopamine (150 mu M). Neither of these effects were exhibited by ascorbic acid, desferal, lisuride, or bromocriptine. Although pergolide exhibited some protection of PC12 c ells against H2O2 toxicity, it was not as potent as apomorphine. In li ght of the present findings and the clinical reports that parkinsonian patients on long-term apomorphine therapy stabilize clinically and ca n be weaned off L-dopa, one may assume that apomorphine can exert a ne uroprotective activity by way of its potent antioxidant properties.