R(-)-DEPRENYL POTENTIATES DOPAMINE-INDUCED CYTOTOXICITY TOWARD CATECHOLAMINERGIC NEUROBLASTOMA SH-SY5Y CELLS

Autoxidation of dopamine or L-DOPA (3,4-dihydroxyphenylalanine) genera tes reactive oxygen species (ROS), i.e., hydrogen peroxide, superoxide , and hydroxyl radical, which are potentially cytotoxic. Increased for mation of ROS has been proposed to be involved in the pathogenesis of many human diseases, including Parkinson's disease. Several reports su ggest that R(-)-deprenyl (an MAO-B inhibitor and anti-Parkinsonian dru g) may directly or indirectly exert antioxidant effects and thus prote ct neurons. We have assessed the toxic effects of dopamine and L-DOPA toward catecholaminergic neuroblastoma SH-SY5Y cells and whether R(-)- deprenyl and several structurally related compounds possess antioxidan t effects in this system, The results show that both dopamine and L-DO PA are quite cytotoxic toward SH-SY5Y cells. R(-)-deprenyl rather than reducing this dopamine-induced toxicity actually enhances it, Structu ral analogues of R(-)-deprenyl, such as 4-methyldeprenyl, (-)-methylam phetamine, and clorgy-line, exhibited similar effects. Some different MAO-B inhibitors, namely, the aliphatic N-methylpropargylamines, e.g., (+/-)-M-2-PP [N-(2-pentyl)-N-methylpropargylamine] and N-[2-hexyl]-N- methylpropargylamine, which can also protect and rescue neurons in sev eral in vivo and in vitro models, did not exacerbate the cytotoxicity of dopamine. Neither R(-)-deprenyl nor (+/-)-M-2-PP affected the L-DOP A-induced cytotoxicity toward SH-SYSY cells. (C) 1997 Academic Press