Abstract

Background

Aliphatic Propargylamines as MAO-B Inhibitors

Neuroprotective and neurorescue effects

Antiapoptotic Properties

Conclusion

Discussion
Board

Several clinical investigations have indicated that R-deprenyl, a typical monoamine oxidase B inhibitor, delay the progression of Parkinson's and Alzheimer's diseases. We found that aliphatic N-methylpropargylamines, such as R-2-heptyl-N-methylpropargylamines (2-HMP), are highly potent, irreversible, selective, MAO-B inhibitors. These compounds do not affect noradrenaline or dopamine uptake and are without an amphetamine-like effect. They are capable of protecting mouse striatal dopamine neurons against MPTP-induced toxicity and against DSP-4-induced depletion of noradrenergic axons in the hippocampus. They rescue hippocampal neurons when they have been damaged by an ischemia insult or by kainic acid in rodents. They block the expressions of HSP70 and delay c-Fos expression in hippocampal CA1 region as elicited by kainic acid. 2-HMP also exhibits a neurorescue effect against neuronal damage in retrosplenial cortex as induced by a high dose of NMDA antagonist MK-801. Confocal microscopy revealed prevention of neuronal damage in hippocampal slices under hypoxia-hypoglycemia conditions. It was proposed that inhibition of MAO-B activity would reduce oxidation of dopamine and subsequently oxidative stress, however, the neurorescue effects can not be attributed to inhibition of MAO-B activity. An anti-apoptotic mechanism has been proposed. The anti-apoptotic effect is, however, not universal, since these drugs do not prevent apoptosis in thymocytes in vitro. The exact mechanism and site of action remain to be established.

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Presentation Number SAyu0398
Keywords: MAO, deprenyl, selegiline, neuroprotection, neurorescue