Experience with tranylcypromine in early Parkinson’s disease

  • S. Fahn
  • S. Chouinard
Part of the Journal of Neural Transmission. Supplement book series (NEURAL SUPPL, volume 52)


A leading hypothesis of the pathogenesis of neuronal degeneration of the substantia nigra dopamine-containing cells in Parkinson’s disease (PD) is excessive oxidative stress. In part, this oxidative stress is the result of the oxidation of dopamine by the action of monoamine oxidases (MAO) A and B to generate hydrogen peroxide and subsequent oxygen free radicals. Because of this hypothesis we have treated patients with early PD, not yet requiring any symptomatic treatment, with tranylcypromine, a drug that inhibits both MAO’s. These patients were required to observe a tyraminerestricted diet. Thirty-seven patients on tranylcypromine have been followed by us for up to 33 months. Four patients discontinued the drug because of pending surgery. Of the remaining 33, six had adverse effects that lead to discontinuation of the drug, mainly impotency in men. Another common adverse effect encountered was insomnia, but this problem was not a cause of stopping the drug. Depression lifted in all five patients who had this problem at the time tranylcypromine was initiated. Only two patients have so far required treatment with levodopa or a dopamine agonist, and this need occurred within the first 6 months of treatment. The evaluation of all 37 patients revealed that parkinsonian symptoms improved slightly on introduction of tranylcypromine as measured by the Unified Parkinson’s Disease Rating Scale, the Hoehn & Yahr Staging Scale, and the Schwab & England Activities of Daily Living Scale. Follow-up evaluations for a minimum of 6 months between the first post-tranylcypromine visit and the most recent visit revealed only slight worsening of parkinsonian signs and symptoms, with a mean interval of almost 1.5 years. A longer period of follow-up is needed to determine how long the severity of PD will remain mild in this group of patients.


Dopamine Agonist Parkinson Study Group Oxidant Stress Hypothesis Yahr Score Selegiline Treatment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington. J Neurol Sci 20:415–455PubMedCrossRefGoogle Scholar
  2. Birkmayer W, Knoll J, Riederer P, Youdim MBH (1983) (—)-deprenyl leads to prolongation of L-dopa efficacy in Parkinson’s disease. Mod Probl Pharmacopsychiatry 19: 170–176PubMedGoogle Scholar
  3. Cohen G (1983) The pathobiology of Parkinson’s disease: biochemical aspects of dopamine neuron senescence. J Neural Transm [Suppl 19]: 89–103Google Scholar
  4. Cohen G (1986) Monoamine oxidase, hydrogen peroxide, and Parkinson’s disease. Adv Neurol 45: 119–125Google Scholar
  5. Fahn S (1989) The endogenous toxin hypothesis of the etiology of Parkinson’s disease and a pilot trial of high dosage antioxidants in an attempt to slow the progression of the illness. Ann NY Acad Sci 570: 186–196PubMedCrossRefGoogle Scholar
  6. Fahn S (1992) A pilot trial of high-dose alpha-tocopherol and ascorbate in early Parkinson’s disease. Ann Neurol 32: S128–S132PubMedCrossRefGoogle Scholar
  7. Fahn S, Cohen G (1992) The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it. Ann Neurol 32: 804–812PubMedCrossRefGoogle Scholar
  8. Fahn S, Duffy P (1977) Parkinson’s disease. In: Goldensohn ES, Appel SH (eds) Scientific approaches to clinical neurology. Lea & Febiger, Philadelphia, pp 1119–1158Google Scholar
  9. Fahn S, Elton RL, Members of the UPDRS Development Committee (1987) The Unified Parkinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M (eds) Recent developments in Parkinson’s disease, vol 2. Macmillan Healthcare Information, Florham Park NJ, pp 153–163, 293–304Google Scholar
  10. Fornstedt B, Pileblad E, Carlsson A (1990) In vivo autoxidation of dopamine in guinea pig striatum increases with age. J Neurochem 55: 655–659PubMedCrossRefGoogle Scholar
  11. Graham DG, Tiffamy SM, Bell WR, Gutknecht WF (1978) Autooxidation versus covalent binding of quinone as the mechanism of toxicity of dopamine, 6-hydro-xydopamine and related compounds toward C1300 neuroblastoma cells in vitro. Mol Pharmacol 14: 644–653PubMedGoogle Scholar
  12. Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17: 427–442PubMedCrossRefGoogle Scholar
  13. Hornykiewicz O (1966) Metabolism of brain dopamine in human parkinsonism: neurochemical and clinical aspects. In: Costa E, Côté LJ, Yahr MD (eds) Biochemistry and pharmacology of the basal ganglia. Raven Press, Hewlett NY, pp 171–185Google Scholar
  14. Hornykiewicz O (1982) Brain neurotransmitter changes in Parkinson’s disease. In: Marsden CD, Fahn S (eds) Movement disorders. Butterworth Scientific, London, pp 41–58Google Scholar
  15. Jenner P (1991) Oxidative stress as a cause of Parkinson’s disease. Acta Neurol Scand 84: 6–15CrossRefGoogle Scholar
  16. Jenner P, Dexter DT, Sian J, Schapira AHV, Marsden CD (1992a) Oxidative stress as a cause of nigral cell death in Parkinson’s disease and incidental Lewy body disease. Ann Neurol 32: S82–S87PubMedCrossRefGoogle Scholar
  17. Jenner P, Schapira AHV, Marsden CD (1992b) New insights into the cause of Parkinson’s disease. Neurology 42: 2241–2250PubMedCrossRefGoogle Scholar
  18. Myllyla VV, Sotaniemi KA, Tuominen J, Heinonen EH (1989) Selegiline as primary treatment in early phase Parkinson’s disease — an interim report. Acta Neurol Scand 126: 177–182CrossRefGoogle Scholar
  19. Olanow CW (1990) Oxidation reactions in Parkinson’s disease. Neurology 40[Suppl 3]: 32–37PubMedGoogle Scholar
  20. Olanow CW (1992) An introduction to the free radical hypothesis in Parkinson’s disease. Ann Neurol 32: S2–S9PubMedCrossRefGoogle Scholar
  21. Parkinson Study Group (1989a) Effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 321: 1364–1371CrossRefGoogle Scholar
  22. Parkinson Study Group (1989b) DATATOP: a multicenter controlled clinical trial in early Parkinson’s disease. Arch Neurol 46: 1052–1060CrossRefGoogle Scholar
  23. Parkinson Study Group (1993) Effects of tocopherol and deprenyl on the progression of disability in early parkinson’s disease. N Engl J Med 328: 176–183CrossRefGoogle Scholar
  24. Parkinson Study Group (1995) Cerebrospinal fluid homovanillic acid in the DATATOP study on Parkinson’s disease. Arch Neurol 52: 237–245CrossRefGoogle Scholar
  25. Parkinson Study Group (1996a) Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP subjects not requiring levodopa. Ann Neurol 39: 29–36CrossRefGoogle Scholar
  26. Parkinson Study Group (1996b) Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP patients requiring levodopa. Ann Neurol 39: 37–45CrossRefGoogle Scholar
  27. Riederer P, Wuketich S (1976) Time course of nigrostriatal degeneration in Parkinson’s disease. J Neural Transm 38: 277–301PubMedCrossRefGoogle Scholar
  28. Schwab RS, England AC Jr (1969) Projection technique for evaluating surgery in Parkinson’s disease. In: Gillingham FJ, Donaldson MC (eds) Third symposium on Parkinson’s disease. E & S Livingstone, Edinburgh, pp 152–157Google Scholar
  29. Spencer JPE, Jenner P, Halliwell B (1995) Superoxide-dependent depletion of reduced glutathione by L-DOPA and dopamine. Relevance to Parkinson’s disease. Neuroreport 6: 1480–1484PubMedCrossRefGoogle Scholar
  30. Tetrud JW, Langston JW (1989) The effect of deprenyl (selegiline) on the natural history of Parkinson’s disease. Science 245: 519–522PubMedCrossRefGoogle Scholar
  31. Zigmond MJ, Hastings TG, Abercrombie ED (1992) Neurochemical responses to 6-hydroxydopamine and L-dopa therapy: implications for Parkinson’s disease. Ann NY Acad Sci 648: 71–86PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • S. Fahn
    • 1
    • 3
  • S. Chouinard
    • 2
  1. 1.Department of NeurologyColumbia University College of Physicians & SurgeonsNew YorkUSA
  2. 2.The Neurological Institute of New YorkPresbyterian HospitalNew YorkUSA
  3. 3.Neurological InstituteNew YorkUSA

Personalised recommendations