Journal of Neural Transmission

, Volume 36, Issue 3–4, pp 303–326 | Cite as

The potentiation of the anti akinetic effect after L-Dopa treatment by an inhibitor of Mao-B, deprenil

  • W. Birkmayer
  • P. Riederer
  • M. B. H. Youdim
  • W. Linauer


The potentiation of the ami akinetic effect after L-Dopa treatment by an inhibitor of monoamine oxidase (MAO) “B”, Deprenil, has been demonstrated in parkinsonian patients with or without previous L-Dopa therapy. Application of the drug has been performed orally, intravenously and intramuscularly. Excellent kinetic effects resulted when combined with Madopar. The combined treatment with L-Dopa was highly effective when applicated i.v. or i.m.

Deprenil is an inhibitor of MAO-B and is characterized by less frequent side effects. These are predominantly involuntary movements and confusion, which can be eliminated by lowering the dosage of Deprenil.

A daily rhythm of MAO could be demonstrated in several areas of human brains as well in a control group as in parkinsonian patients with or without L-Dopa therapy. Maximal activity of MAO occurs between noon and 6 p.m.

The clinical and biochemical data are discussed regarding the off-phenomenons as Deprenil is an excellent drug for preventing these.


Public Health Human Brain Monoamine Combine Treatment Maximal Activity 
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. Anton, A. M., andD. F. Sayre: The distribution of Dopamine and Dopa in various animals and a method for their determination in diverse biological material. J. Pharmacol. Exp. Therap.145, 326 (1964).Google Scholar
  2. Barbeau, A.: Dopamine and basal ganglia disease. Arch. Neurol.4, 97–102 (1961).PubMedGoogle Scholar
  3. Barbeau, A.: The clinical physiology of side effects in long-term L-Dopa therapy. In: Advances in Neurology, Vol. 5, pp. 347–365. New York: Raven Press. 1974.Google Scholar
  4. Bernheimer, H., W. Birkmayer, andO. Hornykiewicz: Verteilung des 5-Hydroxytryptamines (Serotonin) im Gehirn des Menschen und sein Verhalten bei Patienten mit Parkinson-Syndrom. Klin. Wschr.39, 1056 to 1059 (1961).Google Scholar
  5. Bernheimer, H., W. Birkmayer, andO. Hornykiewicz: Verhalten der Monoaminoxydase im Gehirn des Menschen nach Therapie mit Monoaminoxydase-Hemmern. Wr. klin. Wschr.74 (33/34), 558–559 (1962).Google Scholar
  6. Birkmayer, W., andO. Hornykiewicz: Der L-3, 4-Dioxyphenylalanin (L-Dopa) Effekt bei der Parkinson-Akinese. Wr. klin. Wschr.73, 787–788 (1961).Google Scholar
  7. Birkmayer, W., andO. Hornykiewicz: Der Dioxyphenylalanin (L-Dopa) Effekt beim Parkinson-Syndrom des Menschen. Arch. Psych.203, 560 to 571 (1962).Google Scholar
  8. Birkmayer, W., andE. Neumayer: Die moderne medikamentöse Behandlung des Parkinsonismus. Z. Neurol.202, 257–280 (1972).PubMedGoogle Scholar
  9. Birkmayer, W., W. Danielczyk, E. Neumayer, andP. Riederer: L-Dopa Level in Plasma, Primary Condition for the Kinetic Effect. J. Neural Transm.34, 133–143 (1973).PubMedGoogle Scholar
  10. Birkmayer, W., L. Ambrozi, E. Neumayer, andP. Riederer: Longevity in Parkinson's disease treated with L-Dopa. Clin. Neurol. and Neurosurg.1, 15–19 (1974).Google Scholar
  11. Calne, D. B., L. E. Claveria, andJ. G. Allen: Plasma Levodopa and the “On-Off” effect. In: Advances in Neurology, Vol. 5, pp. 341–356, New York: Raven Press. 1974.Google Scholar
  12. Carlsson, A., M. Lindqvist, T. Magnusson, andB. Waldeck: On the presence of 3-hydroxytyramine in brain. Science127, 471 (1958).PubMedGoogle Scholar
  13. Coburn, S. P., M. Seidenberg, andR. W. Fuller: Daily rhythm in plasma tyrosine and phenylalanine. P.S.E.B.M.129, 338–343 (1968).Google Scholar
  14. Collins, G. G. S., M. Sandler, E. D. Williams, andM. B. H. Youdim: Multiple forms of human brain mitochondrial monoamine oxidase. Nature225, 817–820 (1970).PubMedGoogle Scholar
  15. Collins, G. G. S., J. Pryse-Davies, M. Sandler, andJ. Southgate: Effect of pretreatment with Oestradiol, Progesterone and Dopa on monoamine oxidase activity in the rat. Nature226, 642–643 (1970 a).PubMedGoogle Scholar
  16. Danielczyk, W.: Die Behandlung von akinetischen Krisen. Med. Welt24, 1278–1282 (1973).PubMedGoogle Scholar
  17. Davison, A. N.: Physiological role of monoamine oxidase. Physiol. Rev.38, 729 (1958).PubMedGoogle Scholar
  18. Duvoisin, R. C.: Variations in the “On-Off” phenomenon. In: Advances in Neurology, Vol. 5, pp. 339–340. New York: Raven Press. 1974.Google Scholar
  19. Ehringer, H., andO. Hornykiewicz: Verteilung von NA und Dopamin im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin. Wschr.38, 1236–1239 (1960).PubMedGoogle Scholar
  20. Everett, G. M., andR. G. Wiegand: Central amines and behavioural states: a critique and new data. In: Proceedings of the 1st Internat. Pharmacol. Meeting, Vol. 8, Pharmacol. Analysis of central nervous action, pp. 85–92 (Paton, W. D. M., andP. Lindgren, eds.). Oxford: Pergamon Press. 1962.Google Scholar
  21. Fabn, S.: “On-Off” phenomenon with levodopa therapy in parkinsonism. Neurology 1974, 431–441.Google Scholar
  22. Friedman, A. H., andCh. A. Walker: Circadian rhythms in rat mid-brain and caudate nucleus biogeinc amine levels. J. Physiol.197, 77–85 (1968).PubMedGoogle Scholar
  23. Ganrot, P. O., E. Rosengren, andC. G. Gottfries: Effect of Iproniazid on monoamines and monoamine oxidase in human brain. Experientia1816, 260–261 (1962).Google Scholar
  24. Gey, K. F., A. Pleischer, andW. Burkard: Effect of inhibitors of monoamine oxidase on various enzymes and on the storage of monoamines. Annals of the New York Academy of Sciences107, 1147–1151 (1963).PubMedGoogle Scholar
  25. Hanin, I., R. Massarelli, andE. Costa: Acetylcholine concentrations in rat brain: Diurnal oscillation. Science170 (3955), 341–342 (1970).PubMedGoogle Scholar
  26. Holzbauer, M., andM. B. H. Youdim: Monoamine oxidase and Oestrouscycle. Brit. J. pharmacol.48, 600–608 (1973).Google Scholar
  27. Kraml, M.: A rapid microfluorimetric determination of monoamine oxidase. Biochem. Pharmacol.14, 1648–1685 (1965).Google Scholar
  28. Lloyd, K. G., L. Davidson, andO. Hornykiewicz: Metabolism of Levodopa in the human brain. In: Advances in Neurology, Vol. 3, pp. 173–188. New York: Raven Press. 1973.Google Scholar
  29. Lowry, O. H., N. J. Rosebrough, A. L. Farr, andR. J. Randall: Protein measurement with the Folin phenol reagent. J. Biol. Chem.193, 265–275 (1951).PubMedGoogle Scholar
  30. Markham, C.H.: The “On-Off” side effect of L-Dopa. In: Advances in Neurology, Vol. 5, pp. 387–396. New York: Raven Press. 1974.Google Scholar
  31. Merck, E.: Klinisches Labor, 11. Aufl., pp. 128–134. Darmstadt: E. Merck. 1970.Google Scholar
  32. Okada, T., T. Fujita, T. Ohta, T. Kato, K. Ikuta, andT. Nagatsu: A 24-hour rhythm in human serum dopamine-β-hydroxylase activity. Experientia30/6, 605–607 (1974).Google Scholar
  33. Papavasiliou, S., G. C. Cotzias, andI. Mena: Short-and long-term approaches to the “On-Off” phenomenon. In: Advances in Neurology, Vol. 5, pp. 379–386. New York: Raven Press. 1974.Google Scholar
  34. Parvez, H., andS. Parvez: The rate limiting control of enzymes monoamine oxidase and catechol-O-methyl transferase in the foetus and the adult by adreno-cortical hormones. Experientia29, 1259–1262 (1973).PubMedGoogle Scholar
  35. Piepho, R., andA. H. Friedman: Twenty-four hour rhythms in the glycine content of rat hindbrain and spinal cord. Life Sciences10, 1355–1362 (1971).Google Scholar
  36. Quay, W. B.: Differences in circadian rhythms in 5-hydroxy-tryptamine according to brain regions. Am. J. Physiol.215 (6), 1448–1453 (1968).PubMedGoogle Scholar
  37. Riederer, P., W. Birkmayer, E. Neumayer, L. Ambrozi, andW. Linauer: The daily rhythm of HVA, VMA, (VA) and 5-HIAA in depressionsyndrom. J. of Neural Transm.35, 23–45 (1974).Google Scholar
  38. Robinson, D. S., J. M. Davis, A. Nies, C. L. Ravaris, andD. Sylvester: Relation of sex and aging to monoamine oxidase activity of human brain, plasma, and platelets. Arch. Gen. Psychiat.24, 536–539 (1971).PubMedGoogle Scholar
  39. Sandier, M., andM. B. H. Youdim: Monoamine oxidase: the present status. Int. Pharmacopsychiat.9, 27–34 (1974).Google Scholar
  40. Scheving, I., W. H. Harrison, P. Gordon, andJ. E. Pauly: Daily fluctuations (circadian and ultradian) in biogenic amines of the rat brain. American J. Physiol.214 (1), 166–173 (1968).Google Scholar
  41. Sjoerdsma, A., W. Lovenberg, J. A. Oates, J. R. Crout, andS. Udenfriend: Alterations in the pattern of amine excretion in man produced by a monoamine oxidase inhibitor. Science130, 225 (1959).PubMedGoogle Scholar
  42. Spector, S.: Effect of 6-OH-Dopa and L-Dopa on norepinephrine metabolism. In: Monoamines noyaux gris centraux et syndrome de Parkinsons (Symp. Bel-AIR IV, Genève Sept. 1970), pp. 159–163 (de Ajuriaguerra). Genève: G. Gauthier; Paris: Masson.Google Scholar
  43. Spector, S., J. Tarver, andB. Berkowitz: Effects of drugs and physiological factors in the disposition of catecholamines in blood vessels. Pharmacol. Rev.24, 190–202 (1972).Google Scholar
  44. Sweet, R. D., andF. H. McDowell: The “On-Off” response to chronic L-Dopa treatment of parkinsonism. In: Advances in Neurology, Vol. 5, pp. 331–338. New York: Raven Press. 1974.Google Scholar
  45. Tagliamonte, A., R. Gessa, G. Biggio, L. Vargiu, andG. L. Gessa; Daily changes of free serum tryptophan in humans. Life Sciences14, 349–354 (1974).PubMedGoogle Scholar
  46. Weil-Malherbe, H., H. S. Posner, andG. R. Bowles: Changes in the concentration and intracellular distribution of brain catecholamines: the effects of reserpine,β-phenylisopropylhydrazine, pyrogallol and 3, 4-dihydroxyphenylalanine, alone and in combination. J. Pharm. Exp, Ther.732, 278–286 (1961).Google Scholar
  47. Werder, K. V., G. R. Van Loon, F. Yatsu, andP. H. Forsham: Corticosteroid and growth hormones secretion in patients treated with L-dopa. Klin. Wschr.48, 1454 (1970).PubMedGoogle Scholar
  48. Wurtman, R. J., Ch. Chou, andC. M. Rose: Daily rhythm in tyrosine concentration in human plasma: Persistence on low-protein diets. Science158, 660–662 (1967).PubMedGoogle Scholar
  49. Yahr, M. D.: Variations in the “On-Off” Effect. In: Advances in Neurology, Vol. 5, pp. 397–404. New York: Raven Press. 1974.Google Scholar
  50. Youdim, M. B. H., andT. L. Sourkes: The effect of heat, inhibitors and riboflavin deficiency on monoamine oxidase. Can. J. Biochem.43, 1305 to 1318 (1965).Google Scholar
  51. Youdim, M. B. H., G. G. S. Collins, M. Sandier, A. B. Bevan Jones, C. M. B. Pare, andW. J. Nicholson: Human brain monoamine oxidase, multiple forms and selective inhibitors. Nature236, 225–228 (1972).PubMedGoogle Scholar
  52. Youdim, M. B. H., M. Holzbauer, andH. F. Woods: Physico-chemical properties, development and regulation of central and peripheral monoamine oxidase activity. In: Neuropsychopharmacology of monoamines and their regulatory enzymes, pp. 11–28. New York: Raven Press. 1974.Google Scholar
  53. Youdim, M. B. H.: Monoamine oxidase: its inhibition. In: Recent Developments in Genetics and Psychopharmacology. Mod. Probl. Pharmacopsych., Vol. 10, pp. 65–88 (Mendlewicz, J., ed.). Basel: Karger. 1975.Google Scholar
  54. Zigmond, M. J., andR. J. Wurtman: Daily rhythm in the accumulation of brain catecholamines synthesized from circulating H3-tyrosine. J. Pharm. Exp. Ther.172 (2), 416–422 (1970).Google Scholar

Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • W. Birkmayer
    • 1
  • P. Riederer
    • 1
  • M. B. H. Youdim
    • 1
  • W. Linauer
    • 1
  1. 1.Ludwig-Boltzmann-Institut für NeurochemieGeriatrisches Krankenhaus der Stadt Wien-LainzAustria

Personalised recommendations