Affiliations: Neuropsychiatry Research Unit, Department of
Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Note: [] Corresponding author: P.H. Yu, Neuropsychiatry Research Unit,
Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan,
S7N 5E4 Canada. Tel: +1 306 966 8816; Fax: +1 306 966 8830; E-mail:
[email protected]
Abstract: Several clinical investigations have indicated that R-deprenyl, a
typical monoamine oxidas B inhibitor, delays the progression of Parkinson's and
Alzheimer's disease. A number of aliphatic N-methylpropargylamines, such as
R-2-hexyl-N-methylpropargylamines (R-2HxMP), have been found to be highly
potent, irreversible, selective, MAO-B inhibitors both in vitro and in vivo.
These aliphatic propargylamines do not affect noradrenaline of dopamine uptake
and are chemically without an amphetamine moiety and therefore do not exhibit
any amphetamine-like effects. They are capable of protecting mouse striatal
dopamine neurons against MPTP-induced toxicity in the caudate, against
MK-801-induced apoptosis in the retrosplenial cortex and against DSP-4-induced
depletion of naradrenergic axons. They rescue hippocampal neurons in rodents
following kainate-induced neuronal damage. They block the expression of heat
shock protein (HSP70) and delayed c-Fos expression in hippocampal CA1 region
as elicited by kainate. Confocal microscopy also revealed prevention of neuronal
damage in hippocampal slices under hypoxia-hypoglycemia conditions. Aliphatic
N-methylpropargylamines may be useful in the treatment of neurodegenerative
disorders. The mechanism and site of action of the neurorescue effect of these
propargylamines, however, remains to be established.
