Autoxidation of dopamine or L-DOPA (3,4-dihydroxyphenylalanine) generates reactive oxygen species (ROS), i.e., hydrogen peroxide, superoxide, and hydroxyl radical, which are potentially cytotoxic. Increased formation of ROS has been proposed to be involved in the pathogenesis of many human diseases, including Parkinson's disease. Several reports suggest that R(-)-deprenyl (an MAO-B inhibitor and anti-Parkinsonian drug) may directly or indirectly exert antioxidant effects and thus protect 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 antioxidant effects in this system. The results show that both dopamine and L-DOPA are quite cytotoxic toward SH-SY5Y cells. R(-)-deprenyl rather than reducing this dopamine-induced toxicity actually enhances it. Structural analogues of R(-)-deprenyl, such as 4-methyldeprenyl, (-)-methylamphetamine, and clorgyline, 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 several in vivo and in vitro models, did not exacerbate the cytotoxicity of dopamine. Neither R(-)-deprenyl nor (+/-)-M-2-PP affected the L-DOPA-induced cytotoxicity toward SH-SY5Y cells.

1994-01-01·Journal of neural transmission. Supplementum

Is brain superoxide dismutase activity increased following chronic treatment with 1-deprenyl?

Article

作者: Zuo, D. M. ; Lai, C. T. ; Yu, P. H.

L-deprenyl, a specific MAO-B inhibitor, has been proposed to possess a neuroprotective effect. The mechanism of such an effect is unclear. L-Deprenyl has been found to increase rat striatal superoxide dismutase (SOD) activity, which inactivates singlet oxygen. It would be very interesting to know how such activation occurs and whether or not other MAO inhibitors also have such an effect. We have analyzed rat striatal SOD activity using a very sensitive nitrite method and an immunological procedure. The effect of different doses and time of treatment with 1-deprenyl and M-2-PP (2-pentyl-N-methyl-propargylamine), a new highly potent, selective and non-amphetamine-like MAO-B inhibitor, on the rat brain has been investigated. We were unable to detect any increase of SOD activity in the rat striata and cerebral cortex nor any increase in the concentration of immunoreactive SOD antibody in the cortex following chronic treatment with 1-deprenyl and M-2-PP. It remains to be substantiated as to whether or not 1-deprenyl can enhance SOD levels.

1993-01-01·Life sciences3区 · 医学

Chronic effects of monoamine oxidase-B inhibitors on the behaviour of aged mice

3区 · 医学

Article

作者: Alistair J. Barber ; Peter H. Yu ; Alan A. Boulton

In order to measure the chronic effects of monoamine oxidase-B (MAO-B) inhibitors on the physical and cognitive condition of 60 aged male mice, 1-deprenyl or N-methyl-N-(2-pentyl)-propargylamine (M-2-PP) were administered in drinking water (10 micrograms/ml/day) for 37 weeks. The spontaneous open-field locomotion, balancing ability and weight gain of the mice were assessed continuously. At the end of the study the spatial learning ability of all surviving mice was assessed in a Morris water maze. Both drug groups exhibited a reduction in spontaneous locomotion at the same rate as the control group, while there were no changes in balancing ability. The mice receiving 1-deprenyl, however, performed the water maze task less well than the control group. The mice receiving 1-deprenyl also gained weight at a significantly reduced rate compared to both the M-2-PP and water treated groups. A brain MAO assay indicated that MAO-B was completely inhibited by both drugs while MAO-A remained unchanged. The implications of these data on longevity studies using 1-deprenyl and other MAO-B inhibitors are discussed.

100 项与 M-2-PP 相关的药物交易

登录后查看更多信息