The pharmacology of (-)deprenyl

 Birkmayer J
J Neural Transm Suppl 1986; 22:75-89

ABSTRACT

(-)Deprenyl (Selegilinum hydrochloricum, Jumex, Eldepryl) 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).
  • Deprenyl   is an effective antidepressant
  • Deprenyl   in treatment-resistant older depressive patients
  • Deprenyl   + phenylalanine was beneficial in 90% of depression patients
  • Deprenyl   antidepressant effects are by means other than MAO-B inhibition

    Deprenyl   treated rats were much more sexually active

    Deprenyl       enhances sexual performance and longevity in rats

    Deprenyl   may delay the deterioration of neurons during aging
  • Deprenyl   the history of deprenyl
  • Deprenyl   decreases susceptibility to Parkinson's & Alzheimer's disease
  • Deprenyl   restores IGF-1 to youthful levels
  • Deprenyl   protects the vascular endothelium from beta amyloid plaque
  • Deprenyl   reduces cocaine "high"
  • Deprenyl   prolongs animal lifespan by reducing oxidative damage to the brain
  • Deprenyl   may be useful in the treatment of cocaine dependence
  • Deprenyl   increases the life span in Fischer rats
  • Deprenyl   effects on short term memory in young and aged dogs
  • Deprenyl   maintains sexual acitivity in old rats
  • Deprenyl   and Fluoxetine (Prozac) do not interact in combination
  • Deprenyl   prolongs life in elderly dogs
  • Deprenyl   has a cardiac neuroprotective effect
  • Deprenyl   reduces oxidative stress and increases free radical elimination

  • Deprenyl   responses of forebrain neurons to deprenyl

  • Deprenyl   Parkinson's and Alzheimer's patients need 10 mg of deprenyl daily

  • Deprenyl   inhibits tumor growth in rats with mammary tumors

  • Deprenyl   slows the decline of sexual and learning performances in rats

  • Deprenyl   is ten times stronger than methamphetamine as a catecholaminergic

  • Deprenyl   shows favorable results in Tourette's syndrome and narcolepsy

  • Deprenyl   treated rats lived beyond the known maximum lifespan

  • Deprenyl   protects cells from the DNA damage

  • Deprenyl   may protect neurons from ischemic or oxidative damage

  • Deprenyl   prolongs animal lifespan by reducing oxidative damage to the brain

  • Deprenyl   effects on cocaine-induced euphoria

  • Deprenyl   effects on response to experimental cocaine administration  

  • Deprenyl   Are metabolites of deprenyl useful or harmful?

  • Deprenyl   slows the progression of Parkinson's disease

  • Deprenyl   suppresses excitotoxic damage in Parkinson's disease

  • Deprenyl   effect of deprenyl on arm movement in early Parkinson's

  • Deprenyl   effect on cognitive functions in early Parkinson's 

  • Deprenyl   prolongs the life span of Parkinsonian patients significantly

  • Deprenyl   depression in Parkinson's disease

  • Deprenyl   increases the dopamine content of the nerve terminals in Parkinson's

  • 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   slows the death of nigral neurons in Parkinson's disease

  • Deprenyl   + levodopa treated Parkinson's patients live longer

  • Deprenyl   stimulates biosynthesis of cytokines interleukin-1 & 6

  • Deprenyl   effect of MAO-B inhibitors on MPP+ toxicity

  • Deprenyl   modulates the activity of catecholamine-sensitive neurons

  • Deprenyl   improves the performance of patients with Alzheimer's disease

  • Deprenyl   for Alzheimer's disease  

  • Deprenyl   MAO-B inhibitors in the treatment of Alzheimer's disease

  • Deprenyl   in the treatment of Alzheimer's disease

  • Deprenyl   stimulates biosynthesis of cytokines interleukin-1 & 6

  • Deprenyl   and age-related decline of the striatal dopaminergic system

  • Deprenyl   increases dopamine in the striatum of primates

  • Deprenyl   use in treatment-resistant elderly depression patients

  • Deprenyl   protects against neurotoxins

  • Deprenyl   increased rat lifespan by 5%

    Deprenyl   neuroprotective action

    Deprenyl   inhibition of human LDL oxidation

    Deprenyl   facilitates recovery after stroke

 

 

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