Aliphatic N-methylpropargylamines as potential neurorescue agents

Several clinical investigations have indicated that R-deprenyl, a typical m onoamine oxidase B inhibitor, delays the progression of Parkinson's and Alz heimer's diseases. A number of aliphatic N-methylpropargylamines, such as R -2-hexyl-N-methylpropargylamines (R-2HxMP), have been found to be highly po tent, irreversible, selective, MAO-B inhibitors both in vitro and in vivo. These aliphatic propargylamines do not affect noradrenaline or dopamine upt ake and are chemically without an amphetamine moiety and therefore do not e xhibit any amphetamine-like effects. They are capable of protecting mouse s triatal dopamine neurons against MPTP-induced toxicity in the caudate, agai nst MK-801-induced apoptosis in the retrosplenial cortex and against DSP-4- induced depletion of noradrenergic axons. They rescue hippocampal neurons i n rodents following kainate-induced neuronal damage. They block the express ion of heat shock protein (HSP70) and delayed c-Fos expression in hippocamp al CA1 region as elicited by kainate. Confocal microscopy also revealed pre vention of neuronal damage in hippocampal slices under hypoxia-hypoglycemia conditions. Aliphatic N-methylpropargylamines may be useful in the treatme nt of neurodegenerative disorders. The mechanism and site of action of the neurorescue effect of these propargylamines, however, remains to be establi shed.