Monoamine oxidase inhibitors, cognitive functions and neurodegenerative diseases

  • J. C. Delumeau
  • D. Bentué-Ferrer
  • J. M. Gandon
  • R. Amrein
  • S. Belliard
  • H. Allain
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 41)


Recent data obtained in animals and in humans suggest that both MAO-A and MAO-B inhibitors present cognitive enhancing properties of possible interest in the treatment of cognitive disorders. In addition, the rational for using selegiline as a neuroprotector in Parkinson’s disease may also be applicable in Alzheimer’s disease in which a dramatic increase in the MAO-B activity has been reported. It seems then worthwile to investigate the neuroprotective effect of MAOIs in humans and to assess, furthermore, the real therapeutical benefit of their cognitive enhancing properties.


Alzheimer Type Dementia Respiratory Chain Function Demented People Cognitive Enhance Property Mitochondrial Respiratory Chain Function 
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. Allain H, Lieury A, Brunet-Bourgin F, Mirabaud C, Trebon P, Le Coz F, Gandon J-M (1992) Antidepressants and cognition: comparative effects of moclobemide, viloxazine and maprotiline. Psychopharmacology 106: 56–61.CrossRefGoogle Scholar
  2. Amrein R, Allen SR, Güntert TW, Hartmann D, Lorscheid T, Schoerlin M-P, Vranesic D (1989) The pharmacology of monoamine oxidase inhibitors. Br J Psychiatry [Suppl] 6: 66–72.Google Scholar
  3. Anand R, Wesnes KA (1990) Cognition-enhancing effects of moclobemide, a reversible MAO inhibitor in humans. Adv Neurol 51: 261–268.PubMedGoogle Scholar
  4. Baumhackl U, Chan-Palay V, Grüner E, Hebenstreit GF, Kasas A, Katschnig H, Krebs E, Kummer J, Martucci N, Radmayr E, Rieder L, Saletu M, Schlegel S, Lorscheid T (1991) Improvement in cognitive symptoms after treatment with moclobemide in geriatric depressed patients with dementia. Communication at the Congress of the International Psychogeriatric Association, Roma, Italy, August 18-23.Google Scholar
  5. Birkmayer W, Knoll J, Riederer P (1985) Increased life expectancy resulting from addition of L-deprenyl to Madopar treatment in Parkinson’s disease: a long term study. J Neural Transm [Gen Sect] 64: 113–127.CrossRefGoogle Scholar
  6. Byrne E (1992) New concept in respiratory chain diseases. Curr Opin Rheumatol 4: 754–793.Google Scholar
  7. Campi N, Todeschini GP, Scarzella L (1990) Selegiline versus L-acetylcarnitine in the treatment of Alzheimer type dementia. Clin Ther 12: 306–314.PubMedGoogle Scholar
  8. Da Prada M, Kettler R, Burkard WP, Lorez HP, Haefely W (1990a) Some basic aspects of reversible inhibitors of monoamine oxidase-A. Acta Psychiatr Scand [Suppl] 380: 7–12.CrossRefGoogle Scholar
  9. Da Prada M, Kettler R, Keller HH, Burkhard WP, Muggli-Maniglio D, Haefely W (1988) Neurochemical profile of moclobemide, a short-acting and reversible inhibitor of monoamine oxidase-A. J Pharmacol Exp Ther 248: 400–413.Google Scholar
  10. Da Prada M, Kettler R, Keller HH, Cesura AM, Richards JG, Saura M, Muggli-Maniglio D, Wyss P-C, Kyburz E, Imhof R (1990b) From moclobemide to Ro 19-6327 and Ro 41-1049: the development of a new class of reversible, selective MAO-A and MAO-B inhibitors. J Neural Transm [Suppl] 29: 279–292.Google Scholar
  11. Falsaperla A, Preti AM, Oliani C (1990) Selegiline versus oxiracetam in patients with Alzheimer-Type Dementia. Clin Ther 12: 376–384.PubMedGoogle Scholar
  12. Goad DL, Davis CM, Liem P, Fuselier C, McCormack JR, Olsen KM (1991) The use of selegiline in Alzheimer’s patients with behavior problems. J Clin Psychiatry 52: 342–354.PubMedGoogle Scholar
  13. Hebenstreit GF, Baumhackl U, Chan-Palay V, Grüner E, Hebenstreit, Kasas A, Katschnig H, Krebs E, Kummer J, Martucci N, Radmayr E, Rieder L, Saletu M, Schlegel S, Lorscheid T (1991) The treatment of depression in geriatric depressed and demented patients by moclobemide: results from the international multicenter double blind placebo controlled trial. Communication at the Congress of the International Psychogeriatric Association, Roma, Italy, August 18–23.Google Scholar
  14. Ikebe S, Tanaka M, Ohno K, Sato W, Hattori K, Kondo T, Mizuno Y, Ozawa T, (1990) Increase of deleted mitochondrial DNA in the striatum in Parkinson’s disease and senescence. Biochem Biophys Res Commun 170: 1044–1048.PubMedCrossRefGoogle Scholar
  15. Johnston JP (1968) Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol 17: 1285–1287.PubMedCrossRefGoogle Scholar
  16. Klimek V, Nowak G, Zak J, Maj J (1990) The effect of repeated treatments with brofaromine, moclobemide and deprenyl on alpha 1-adrenergic and dopaminergic receptors in the rat brain. Neurosci Lett 108: 189–194.PubMedCrossRefGoogle Scholar
  17. Knoll J (1988) The striatal dopamine dependency on life span in males rats: longevity study with selegiline. Mech Ageing Dev 46: 237–262.PubMedCrossRefGoogle Scholar
  18. Lees AJ, Frankel J, Eatough V, Stern GM (1989) New approaches in the use of selegiline for the treatment of Parkinson’s disease. Acta Neurol Scand 126: 139–145.CrossRefGoogle Scholar
  19. Mann UM, Cooper JM, Krige D, Daniel SE, Schapira AHV, Marsden CD (1992) Brain skeletal muscle and platelet homogenate mitochondrial dysfunction in Parkinson’s disease. Brain 115: 333–342.PubMedCrossRefGoogle Scholar
  20. Martin JR, Schaffner R, Remennik L, Vincent GP, Sepinwall J, Lorez HP, Heafely WE (1989) Cognitive performances enhancing effects of the reversible MAO-inhibitor moclobemide in animals. In: Wurtman RJ, Corkin S, Growdon JH, Ritter-Walker E (eds) Alzheimer’s disease. Center for Brain Science and Metabolism Charitable Trust, Cambridge/Mass., pp 689–694.Google Scholar
  21. McClelland GR, Wesnes K, Jamieson VL, Simpson PM, Christmas L (1988) A double-blind, latin square design study to investigate the effects of single oral doses of 100 and 300 mg moclobemide (Ro 11-1163) compared with placebo and trazodone (100 mg) on psychomotor performance in healthy volunteers, alone and in combination with ethanol (unpublished).Google Scholar
  22. Monteverde A, Gnemmi P, Rossi F, Monteverde A (1990) Selegiline in the treatment of mild to moderate Alzheimer type dementia. Clin Ther 12: 306–314.Google Scholar
  23. O’Caroll AM, Bardsley ME, Tipton KF (1986) The oxydation of adrenaline and noradrenaline by the two forms of monoamine oxydase from human and rat brain. Neurochem Int 8: 493–500.CrossRefGoogle Scholar
  24. Piccini GL, Finali G, Piccirilli M (1990) Neuropsychological effects of L-deprenyl in Alzheimer’s dementia. Clin Pharmacol 14: 147–163.Google Scholar
  25. Riederer P, Konradi C, Hebenstreit G, Youdim MBH (1989) Neurochemical perspectives to the function of monoamine oxidase. Acta Neurol Scand 126: 41–45.CrossRefGoogle Scholar
  26. Schoffner JM, Watts RL, Juncos JL, Torroni A, Wallace DC (1991) Mitochondrial oxidative phosphorylation defects in Parkinson’s disease. Ann Neurol 30: 332–339.CrossRefGoogle Scholar
  27. Slater TF (1984) Free-radical mechanisms in tissue injury. Biochem J 222: 1–15.PubMedGoogle Scholar
  28. Tariot PN, Cohen R, Sunderland T, Newhouse PA, Yount D, Mellow AM, Weingartner H, Mueller EA, Murphy DL (1987a) L-deprenyl in Alzheimer’s disease. Arch Gen Psychiatry 44: 427–433.PubMedCrossRefGoogle Scholar
  29. Tariot PN, Sunderland T, Weingartner H, Murphy DL, Welkowitz JA, Thompson K, Cohen RM (1987b) Cognitive effects of L-deprenyl in Alzheimer’s disease. Psychopharmacology 91: 489–495.PubMedCrossRefGoogle Scholar
  30. Tariot PN, Sunderland T, Cohen R, Newhaouse PA, Mueller EA, Murphy DL (1988) Tranylcypromine compared with L-deprenyl in Alzheimer’s disease. J Clin Psy-chopharmacol 8: 23–27.Google Scholar
  31. Tetrud JW, Langston JW (1987) R-(-)-deprenyl as a possible protective agent in Parkinson’s disease. J Neural Transm [Suppl] 25: 69–79.Google Scholar
  32. Tetrud JW, Langston JW (1989) The effect of deprenyl (selegiline) on the natural history of Parkinson’s disease. Science 245: 519–522.PubMedCrossRefGoogle Scholar
  33. The Parkinson’s Study Group (1989a) Effects of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 321: 1363–1371.Google Scholar
  34. The Parkinson’s Study Group (1989b) DATATOP: a multicenter controlled clinical trial in early Parkinson’s disease. Arch Neurol 46: 1052–1060.CrossRefGoogle Scholar
  35. Trounce I, Byrne E, Marzuki S (1989) Decline in skeletal muscle mitochondrial respiratory chain function: possible factor in ageing. Lancet i: 637–639.CrossRefGoogle Scholar
  36. Wesnes KA, Simpson PM, Christmas L, McClelland GR, Joiner IM (1988) Acute cognitive effects of moclobemide and trazodone, alone and in combination with alcohol, in the elderly. Presentation at British Pharmacological Society, 1988 (unpublished).Google Scholar
  37. Wesnes KA, Simpson PM, Christmas L, Anand R, McClelland GR (1989) The effects of moclobemide on cognition. J Neural Transm [Suppl] 28: 91–102.Google Scholar
  38. Youdim MBH (1983) Implication of MAO-A and MAO-B inhibition for antidepressant therapy. Mod Probi Pharmacopsychiatry 19: 63–74.Google Scholar
  39. Zornettzer ST (1985) Catecholamine system involvement in age-related memory dysfunction. Ann NY Acad Sci 444: 242–254.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • J. C. Delumeau
    • 1
  • D. Bentué-Ferrer
    • 1
  • J. M. Gandon
    • 2
  • R. Amrein
    • 3
  • S. Belliard
    • 1
  • H. Allain
    • 1
  1. 1.Laboratory of Experimental and Clinical PharmacologyUniversity HospitalRennes CedexFrance
  2. 2.Biotrial, Rue Jean PeckerTechnopole Rennes-AtalanteRennesFrance
  3. 3.Pharma Clinical Research CNSF. Hoffmann-La Roche Ltd.BaselSwitzerland

Personalised recommendations