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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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  • Deprenyl  in the treatment of Alzheimer's disease
  • Deprenyl  MAO-B inhibitors in the treatment of Alzheimer's disease
  • Deprenyl  for Alzheimer's disease
  • Deprenyl  stimulates biosynthesis of cytokines interleukin-1 & 6
  • Deprenyl  and age-related decline of the striatal dopaminergic system
  • Deprenyl  improves memory in amnesic Alzheimer's patients
  • Deprenyl  treatment of behavioral symptoms of Alzheimer's disease
  • Deprenyl   increases life span in Parkinson's patients
  • Deprenyl   possible mechanisms of action in Parkinson's disease
  • Deprenyl   effect on arm movement in early Parkinson's
  • Deprenyl   effect on cognitive functions in early Parkinson's 
  • Deprenyl   possible mechanisms of action in Parkinson's
  • Deprenyl   depression in Parkinson's disease
  • Deprenyl   improves visuo-motor control in early Parkinsonism
  • Deprenyl   management of early Parkinson's disease
  • Deprenyl   delays the onset of disability in Parkinsonian patients
  • Deprenyl   and tocopherol antioxidative therapy of Parkinsonism
  • Deprenyl   treatment and death of nigral neurons in Parkinson's disease.
  • Deprenyl   rationale for deprenyl medication in Parkinson's disease
  • Deprenyl   and levodopa in Parkinson's disease
  • Deprenyl   is an MAO-B inhibitor
  • Deprenyl   facilitates neuronal growth without inhibiting monoamine oxidase
  • Deprenyl   pharmacology
  • Deprenyl   biochemical actions
  • Deprenyl   effect of MAO-B inhibitors on MPP+ toxicity
  • Deprenyl   the history of its development
  • Deprenyl   protects neurons against neurotoxins
  • Deprenyl   in neurodegenerative disorders
  • Deprenyl   enhances the release of dopamine
  • Deprenyl   plus L-phenylalanine in the treatment of depression
  • Deprenyl   in the treatment-resistant of older depressive patients
  • Deprenyl   effects in atypical depressives
  • Deprenyl   up-regulates superoxide dismutase and catalase
  • Deprenyl   immunostimulant
  • Deprenyl   pharmacology
  • Deprenyl   effect on rat longevity and sexual acitivity
  • Deprenyl   effects of experimental cocaine administration
  • Deprenyl   effects on longevity in animals
  • Deprenyl   effects on subjective ratings of cocaine-induced euphoria
  • Deprenyl   increases the life span in Fischer rats
  • Deprenyl   effects on short term memory in young and aged dogs
  • Deprenyl   the facilitation of dopaminergic activity in the aged brain
  • Deprenyl   fluoxetine (Prozac) and deprenyl
  • Deprenyl   improves cardiac sympathetic terminal function in heart failure
  • Deprenyl   effect on dopamine concentration in the striatum of a primate
  • Deprenyl   a review of the pharmacology
  • Deprenyl   restores IGF-1 levels to young levels
  • Deprenyl   prolongs life in elderly dogs
  • Deprenyl   past, present, and future
  • Deprenyl   relevance to humans
  • Deprenyl   responses of forebrain neurons to deprenyl
  • Deprenyl   protects neurons from glutamate toxicity
  • Deprenyl   nitric oxide production and dilation of cerebral blood vessels
  • Deprenyl   modulates the decline of the striatal dopaminergic system
  • Deprenyl   inhibits tumor growth in rats with mammary tumors
  • Deprenyl   a catecholaminergic activity enhancer in the brain
  • Deprenyl   releases coupling in the catecholaminergic neurons
  • Deprenyl   clinical potential in neurologic and psychiatric disorders
  • Deprenyl   protects human dopaminergic neuroblastoma cells
  • Deprenyl   nitric oxide production and dilation of cerebral blood vessels
  • Deprenyl   assessing the effects of deprenyl on longevity of animals
  • Deprenyl   effects on cocaine-induced euphoria
  • Deprenyl   effects on response to experimental cocaine administration  
  • Deprenyl   Are metabolites of deprenyl useful or harmful?
  • Deprenyl   is devoid of amphetamine-like effects
  • Deprenyl   treated rats lived beyond the known maximum lifespan
  • Deprenyl   stimulates biosynthesis of cytokines interleukin-1 & 6
  • Deprenyl   pharmacological basis of the beneficial effects
  • Deprenyl   modulates the decline of the dopamineric system