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The pharmacology of (-)deprenyl

Birkmayer J

J Neural Transm Suppl 1986; 22:75-89

ABSTRACT

(-)Deprenyl (Selegiline) developed in the early sixties as a new spectrum, potent, irreversible MAO blocker (Knoll et al., 1965) was introduced as the first selective inhibitor of B-type MAO (Knoll and Magyar, 1972).  In striking contrast to MAO inhibitors which strongly potentiate the pressor effect of tyramine, (-)deprenyl was described to inhibit the tyramine-induced release of noradrenaline in vascular smooth muscle (Knoll et al., 1968).  The peculiar pharmacological spectrum of (-)deprenyl allowed its use as an adjuvant to the levodopa therapy of Parkinson's disease (for review see Birkmayer and Riederer, 1985). Levodopa therapy revolutionized the medication of Parkinson's disease, but severe side-effects forced the search for adjuvants with a levodopa-sparing effect. Peripheral decarboxylase inhibitors are now efficiently used for this purpose. It was reasonable to expect further potentiation and prolongation of the effect of levodopa in parkinsonians with concurrent administration of MAO inhibitors.  A number of irreversible inhibitors of this type were tested in combination with levodopa, and potentiation of the antiakinetic effect of the latter was demonstrated; however, the supervention of distressing side-effect (greatly increased involuntary movements, hypertensive reactions, toxic delirium) terminated any further work along this line. There was a concensus that to give MAO inhibitors concurrently with levodopa was contra-indicated. This conclusion was called in question, however, by the development of deprenyl. (-)Deprenyl is a safe MAO inhibitor which can be given concurrently with levodopa and a peripheral decarboxylase inhibitor for the long run without the supervention of any distressing side-effects.  For details regarding the pharmacology of (-)deprenyl we refer a number of reviews (Knoll 1976, 1978, 1980, 1982, 1983, 1986).  The aim of this paper is to give a brief survey of the most important experimental data which demonstrate that (-)deprenyl facilitates dopaminergic tone in the brain in a peculiar manner and gives a satisfactory explanation for the observation that long-term (-)deprenyl treatment prolongs the life span of Parkinsonian patients significantly (Birkmayer et al., 1985).
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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