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

Acta Neurol Scand Suppl. 1983:95:57-80. doi: 10.1111/j.1600-0404.1983.tb01517.x.

Abstract

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.

Publication types

  • Historical Article

MeSH terms

  • Aging
  • Animals
  • Brain / drug effects
  • Depression / drug therapy
  • Dopamine / physiology
  • Drug Evaluation
  • History, 20th Century
  • Humans
  • Male
  • Monoamine Oxidase Inhibitors / therapeutic use
  • Neurons / drug effects
  • Parkinson Disease / drug therapy
  • Phenethylamines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Selegiline / history
  • Selegiline / pharmacology*
  • Selegiline / therapeutic use
  • Sexual Behavior / drug effects

Substances

  • Monoamine Oxidase Inhibitors
  • Phenethylamines
  • Selegiline
  • Dopamine