Neuroprotective actions of deprenyl.

Ebadi M, Sharma S, Shavali S, El Refaey H.

Department of Pharmacology,
Physiology, and Therapeutics
University of North Dakota School of Medicine and Health Sciences Grand Forks, North Dakota 58203, USA
mebadi@medicine.nodak.edu
J Neurosci Res 2002 Feb 1;67(3):285-9

Abstract

Deprenyl, a selective inhibitor of monoamine oxidase-B (MAO-B), was one of the first adjunct therapies in clinical neurology.  A retrospective analysis of data from patients with Parkinson's disease found a significant increase in survival in those treated with deprenyl plus L-dopa compared with L-dopa alone. The mechanism of action of deprenyl is complex and cannot be explained solely by its MAO-B inhibitory action.  Pretreatment with deprenyl can protect neurons against a variety of neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), 6-hydroxydopamine, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), methyl-beta-acetoxyethyl-2-chloroethylamine (AF64A), and 5,6-dihydroxyserotonin, which damage dopaminergic, adrenergic, cholinergic, and sertoninergic neurons, respectively.  Deprenyl produces an amphetamine-like effect, enhances the release of dopamine, and blocks the reuptake of dopamine.  It stimulates gene expression of L-aromatic amino acid decarboxylase, increases striatal phenylethylamine levels, and activates dopamine receptors.  Deprenyl reduces the production of oxidative radicals, up-regulates superoxide dismutase and catalase, and suppresses nonenzymatic and iron-catalyzed autooxidation of dopamine.  Deprenyl compensates for loss of target-derived trophic support, delays apoptosis in serum-deprived cells, and blocks apoptosis-related fall in the mitochondrial membrane potential.  Most of the aforementioned properties occur independently of deprenyl's efficacy to inhibit MAO-B.

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