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Effects of monoamine oxidase inhibition by selegiline on concentrations of noradrenaline and monoamine metabolites in CSF of patients with Alzheimer's disease

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Journal of Neural Transmission - Parkinson's Disease and Dementia Section

Summary

A double-blind, cross-over trial with 12 patients with Alzheimer's disease (AD) was carried out primarily to test the suitability of this design in the investigation of the clinical, effects of selegiline (10 mg/day) in AD. Cerebrospinal fluid (CSF) samples for the determination of concentrations of noradrenaline (NA) and several monoamine metabolites were collected at baseline and at the end of both four-week treatment periods (placebo and selegiline). The severity of dementia was assessed using Ferm's and Gottfries-Bråne-Steen (GBS) dementia scales. The concentrations of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and the NA metabolites, 3,4-dihydroxyphenylglycol (DHPG), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) decreased significantly during selegiline treatment. There was a clear trend of reduction in concentrations of homovanillic acid (HVA) during selegiline treatment, whereas the concentrations of NA, 5-hydroxyindoleacetic acid (5-HIAA), and tryptophan did not differ significantly. The study design was not suitable for the analysis of the clinical results as there was a significant carry-over effect in both scales. As only the first period data could be used in the analysis, there were no significant differences in the scores of Ferm's or GBS scales, but clear positive trends could be detected in favour of selegiline.

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References

  • Adolfsson R, Gottfries CG, Oreland L, Wiberg A, Winblad B (1980) Increased activity of brain and platelet monoamine oxidase in dementia of Alzheimer's disease. Life Sci 27: 1029–1034

    Article  PubMed  Google Scholar 

  • Agnoli A, Martucci N, Fabbrini G, Buckley AE, Fioravanti M (1990) Monoamine oxidase and dementia: treatment with an inhibitor of MAO-B activity. Dementia 1: 109–114

    Google Scholar 

  • Baraczka F, Fekete MIK, Kanyicska B (1983) Changes in dopamine and 2,3-dihydroxyphenylacetic acid (DOPAC) levels in human cerebrosphinal fluid after L-dopa and deprenyl administration. J Neural Transm 58: 299–304

    Article  PubMed  Google Scholar 

  • Campi N, Todeschini GP, Scarzella L (1990) Selegiline versus L-acetylcarnitine in the treatment of Alzheimer-type dementia. Clin Ther 12(4): 306–314

    PubMed  Google Scholar 

  • Collis MG, Shepherd JT (1980) Interaction of the tricyclic antidepressant amitriptyline with prejunctional alpha and muscarinic receptors in the dog saphenous vein. J Pharmacol Exp Ther 213: 616–622

    PubMed  Google Scholar 

  • Eisler T, Teräväinen H, Nelson R, Krebs H, Weise V, Chem BS, Lake CR, Ebert MH, Whetzel N, Murphy DL, Kopin IJ, Calne DB (1981) Deprenyl in Parkinson's disease. Neurology 31: 19–23

    PubMed  Google Scholar 

  • Falsaperla A, Preti PAM, Oliani C (1990) Selegiline versus oxiracetam in patients with Alzheimer-type dementia. Clin Ther 12(5): 376–384

    PubMed  Google Scholar 

  • Ferm L (1974) Behavioural activities in demented geriatric patients. Geront Clin 16: 185–194

    PubMed  Google Scholar 

  • Finali G, Piccirilli M, Oliani C, Piccinin GL (1991) L-Deprenyl therapy improves verbal memory in amnesic Alzheimer patients. Clin Neuropharmacol 14(6): 523–536

    PubMed  Google Scholar 

  • Glover V, Sandler M, Owern F, Riley GJ (1977) Dopamine is a monoamine oxidase substrate in man. Nature 265: 80–81

    Article  PubMed  Google Scholar 

  • Glover V, Pycock CJ, Sandler M (1983) Tyramine-induced noradrenaline release from rat brain slices: prevention by (−)-deprenyl. Br J Pharmacol 80: 141–148

    PubMed  Google Scholar 

  • Gottfries C-G, Bråne G, Gullberg B, Steen G (1982) A new rating scale for dementia syndromes. Arch Gerontol Geriatr 1: 311–330

    Article  PubMed  Google Scholar 

  • Heinonen EH, Rinne UK (1989) Selegiline in the treatment of Parkinson's disease. Acta Neurol Scand 80 [Suppl]: 103–111

    PubMed  Google Scholar 

  • Heinonen EH, Myllylä V, Sotaniemi K, Lammintausta R, Salonen J, Anttila M, Savijärvi M, Kotila M, Rinne UK (1989) Pharmacokinetics and metabolism of selegiline. Acta Neurol Scand 80 [Suppl]: 93–99

    Google Scholar 

  • Hildebrand J, Bourgeois F, Buyse M, Przedborski S, Goldman S (1990) Reproducibility of monoamine metabolite measurements in human cerebrospinal fluid. Acta Neurol Scand 81: 427–430

    PubMed  Google Scholar 

  • Hovevey-Sion D, Kopin IJ, Stull RW, Goldstein DS (1989) Effects of monoamine oxidase inhibitors on levels of catechols and homovanillic acid in striatum and plasma. Neuropharmacology 28: 791–797

    Article  PubMed  Google Scholar 

  • Izzo JL Jr, Thompson DA, Horowitz D (1985) Plasma dihydroxy-phenylglycol (DHPG) in the in-vivo assessment of human neuronal norepinephrine metabolism. Life Sci 37: 1033–1038

    Article  PubMed  Google Scholar 

  • Jovoy-Agid F, Agid Y (1980) Is the mesocortical dopaminergic system involved in Parkinson's disease? Neurology 30: 1326–1330

    PubMed  Google Scholar 

  • Knoll J (1978) The possible mechanism of action of (−)-deprenyl in Parkinson's disease. J Neural Transm 43: 177–198

    Article  PubMed  Google Scholar 

  • Mangoni A, Grassi MP, Frattola L, Piolti R, Bassi S, Motta A, Marcone A, Smirne S (1991) Effects of a MAO-B inhibitor in the treatment of Alzheimer's disease. Eur Neurol 31: 100–107

    PubMed  Google Scholar 

  • Martignoni E, Bono G, Blandini F, Sinforiani E, Merlo P, Nappi G (1991) Monoamines and related metabolite levels in the cerebrospinal fluid of patients with dementia of Alzheimer type. Influence of treatment with L-deprenyl. J Neural Transm [PD-Sect] 3: 15–25

    Article  Google Scholar 

  • Martini E, Pataky I, Szilágyi K, Venter V (1987) Brief information on an early phase-II study with deprenyl in demented patients. Pharmacopsychiatry 20: 256–257

    PubMed  Google Scholar 

  • McKhan G Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: report of NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology (NY) 34: 939–944

    Google Scholar 

  • Mishima S, Myahara H, Suzuki H (1984) Transmitter release modulated by alphaadrenoceptor antagonists in the rabbit mesenteric artery: a comparison between noradrenaline outflow and electrical activity. Br J Pharmacol 83: 537–547

    PubMed  Google Scholar 

  • Monteverde A, Gnemmi P, Rossi F, Monterverde A, Finali GC (1990) Selegiline in the treatment of mild to moderate Alzheimer-type dementia. Clin Ther 12(4): 315–322

    PubMed  Google Scholar 

  • Piccinin GL, Finali G, Piccirilli M (1990) Neuropsychological effects of 1-deprenyl in Alzheimer's type dementia. Clin Neuropharmacol 13: 147–163

    PubMed  Google Scholar 

  • Riederer P, Youdim MBH, Rausch WD, Birkmayer W, Jellinger K, Seemann D (1978) On the mode of action of 1-deprenyl in the human central nervous system. J Neural Transm 43: 217–226

    Article  PubMed  Google Scholar 

  • Riederer P, Konradi C, Schay V, Kienzl E, Birkmayer G, Danielczyk W, Sofic E, Youdim MBH (1986) Localization of MAO-A and MAO-B in human brain: a step in understanding the, therapeutic action of 1-deprenyl. In: Yahr MD, Bergmann KJ (eds) Parkinson's disease. Raven Press, New York, pp 111–118 (Adv Neurol, vol 45)

    Google Scholar 

  • Rinne UK, Siirtola T, Sonninen V (1978) L-deprenyl treatment of on-off phenomena in Parkinson's disease. J Neural Transm 43: 253–262

    Article  PubMed  Google Scholar 

  • Scheinin M, Chang W-H, Kirk KL, Linnoila M (1983) Simultaneous determination of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluid with high-performance liquid chromatogaphy using electrochemical detection. Anal Biochem 131: 246–253

    Article  PubMed  Google Scholar 

  • Scheinin M, Karhuvaara S, Ojala-Karlsson P, Kallio A, Koulu M (1991) Plasma 3,4-dihydroxyphenylglycol (DHPG) and 3-methyoxy-4-hydroxyphenylglycol (MHPG) are insensitive indicators of α2-adrenoceptor mediated regulation of norepinephrine release in healthy human volunteers. Life Sci 49: 75–84

    Article  PubMed  Google Scholar 

  • Schneider LS, Pollock VE, Zemansky MF, Gleason RP, Palmer R, Sloane B (1991) A pilot study of low-dose L-deprenyl in Alzheimer's disease. J Geriatr Psychiatry Neurol 4: 143–148

    PubMed  Google Scholar 

  • Sunderland T, Tariot PN, Cohen RM, Newhouse PA, Mellow AM, Mueller EA, Murphy DL (1987) Dose-dependent effects of deprenyl on CSF monoamine metabolites in patients with Alzheimer's disease. Psychopharmacology 91: 293–296

    Article  PubMed  Google Scholar 

  • Suzuki O, Matsumoto T (1985) Normetanephrine and metanephrine oxidized by both types of monoamine oxidase. Experimentia 41: 634–636

    Article  Google Scholar 

  • Tariot PN, Cohen RM, 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

    PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Tetrud JW, Langston JW (1989) The effect of deprenyl (selegiline) on the natural history of Parkinson's disease. Science 245: 519–522

    PubMed  Google Scholar 

  • The Parkinson Study Group (1989) Effect of deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med 321: 1364–1371

    Google Scholar 

  • Zsilla G, Knoll J (1982) The action of (−)deprenyl on monoamine turnover rate in rat brain. In: Costa E, Racagni G (eds) Typical and atypical antidepressants: molecular mechanisms. Raven Press, New York, pp 211–217

    Google Scholar 

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Author notes

  1. E. H. Heinonen M. D.

    Present address: Orion Corporation FARMOS, R & D Pharmaceuticals, P. O. Box 425, SF-20101, Turku, Finland

Authors and Affiliations

  1. Koskela Hospital, Helsinki, University of Turku, Turku, Finland

    M. Savijärvi & M. Kotila

  2. Department of Pharmacology, University of Turku, Turku, Finland

    M. Scheinin

  3. Orion Corporation FARMOS, R & D Pharmaceuticals, P. O. Box 425, SF-20101, Turku, Finland

    A. Hajba

Authors
  1. E. H. Heinonen M. D.
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  2. M. Savijärvi
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  3. M. Kotila
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  4. A. Hajba
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  5. M. Scheinin
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Heinonen, E.H., Savijärvi, M., Kotila, M. et al. Effects of monoamine oxidase inhibition by selegiline on concentrations of noradrenaline and monoamine metabolites in CSF of patients with Alzheimer's disease. J Neural Transm Gen Sect 5, 193–202 (1993). https://doi.org/10.1007/BF02257674

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  • DOI: https://doi.org/10.1007/BF02257674

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