Deprenyl (selegiline): the history of its development and pharmacological action.

Knoll J.

Acta Neurol Scand Suppl 1983;95:57-80


Deprenyl inhibits MAO-B selectively in different animal species and in man.  Its safety margin is remarkable. We were able to block MAO-B activity in the brain selectively in vivo in four species (mouse, rat, cat, dog) with s.c. administration of 0.17-0.31% of LD50.  The usual oral dose range in clinical practice, 5-20 mg daily (0.05-0.2 mg/kg), is about ten times lower than the orally active dose in the rat. Deprenyl proved to be safe drug in man. Neither hypertensive reactions nor the need for any special dietary care were ever encountered during long-term (2-8 years) daily administration of the drug.  The most important effect of deprenyl in the brain is the sensitization of dopaminergic neurons to physiological and pharmacological influences, but in contrast to levodopa or bromocrytine, deprenyl does not elicit an acute increase in dopaminergic activity.  The effect of deprenyl is due, on the one hand, to the inhibition of MAO-B and, on the other hand, to inhibition of the uptake of dopamine. In agreement with its peculiar spectrum of pharmacological activity, deprenyl proved to be a useful adjuvant to levodopa alone or in combination with a peripheral decarboxylase inhibitor. In addition, a supplement of deprenyl in Parkinson's disease led to significant prolongation of the duration of the illness. This has not been observed so far with other antiparkinsonian drugs. The dopamine content of the human caudate nucleus decreases by 13% per decade over the age of 45. The hypothesis has been put forward that the significant increase of incidence of depression in the elderly, the age-dependent decline in male sexual vigour and the frequent appearance of parkinsonian symptoms in the later decades of life might be attributed to a decrease of dopamine and 'trace amines' in the brain. The possibility of countering these biochemical lesions of ageing by long-term administration of deprenyl, a selective inhibitor of MAO-B which facilitates dopaminergic and 'trace-aminergic' activity in the brain, and is a safe drug in man, is considered in detail.

  • 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