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Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (clorgyline) or MAO-B (selegiline and pargyline)

  • D. L. Murphy
  • F. Karoum
  • D. Pickar
  • R. M. Cohen
  • S. Lipper
  • A. M. Mellow
  • P. N. Tariot
  • T. Sunderland
Part of the Journal of Neural Transmission. Supplement book series (NEURAL SUPPL, volume 52)

Summary

Marked, dose-dependent elevations in the urinary excretion of phenylethylamine, para-tyramine, and meta-tyramine were observed in depressed patients treated for three or more weeks with 10, 30, or 60 mg/ day of the partially-selective inhibitor of MAO-B, selegiline (1-deprenyl). In comparative studies with other, structurally similar acetylenic inhibitors of MAO, pargyline, an MAO-B > MAO-A inhibitor used in doses of 90mg/day for three or more weeks, produced elevations in these trace amines which were similar to those found with the highest dose of selegiline studied. Clorgyline, a selective inhibitor of MAO-A used in doses of 30mg/ day for three or more weeks (a dose/time regimen previously reported to reduce urinary, plasma, and cerebrospinal fluid 3-methoxy-4hydroxyphenylethyleneglycol (MHPG) > 80%, indicating a marked inhibitory effect on MAO-A in humans in vivo) produced negligible changes in trace amine excretion. In comparison to recent studies of individuals lacking the genes for MAO-A, MAO-B, or both MAO-A and MAO-B, the lack of change in trace amine excretion in individuals with a mutation affecting only MAO-A is in agreement with the observed lack of effect of clorgyline in the present study. Selegiline produced larger changes in trace amines — at least at the higher doses studied — than found in individuals lacking the gene for MAO-B, in agreement with other data suggesting a lesser selectivity for MAO-B inhibition when selegiline was given in doses higher than 10mg/day. Overall, trace amine elevations in individuals receiving the highest dose of deprenyl or receiving pargyline were approximately three to five-fold lower than the elevations observed in individuals lacking the genes for both MAOA and MAO-B, suggesting that these drug doses yield incomplete inhibition of MAO-A and MAO-B.

Keywords

Monoamine Oxidase Trace Amine Deficient Subject Norrie Disease Inhibitor Clorgyline 
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.

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References

  1. Boulton AA (1978) The tyramines: functionally significant biogenic amines or metabolic accident. Life Sci 23: 659–672PubMedCrossRefGoogle Scholar
  2. Celada P, Artigas F (1993) Monoamine oxidase inhibitors increase preferentially extracellular 5-hydroxytryptamine in the midbrain raphe nuclei. A brain microdialysis study in the awake rat. Naunyn Schmiedebergs Arch Pharmacol 347: 583–590PubMedCrossRefGoogle Scholar
  3. Davis BA, Boulton AA (1994) The trace amines and their acidic metabolites in depression — an overview. Prog Neuropsychopharmacol Biol Psychiatry 18: 17–45PubMedCrossRefGoogle Scholar
  4. de la Chapelle A, Sankila E-M, Lindlof M, Aula P, Norio R (1985) Norrie disease caused by a gene deletion allowing carrier detection and prenatal diagnosis. Clin Genet 28: 317–320PubMedCrossRefGoogle Scholar
  5. Eisler T, Teravainen H, Nelson R, Krebs H, Weise V, Lake CR, Ebert MH, Whetzel N, Murphy DL, Kopin IJ, Calne DB (1981) Deprenyl in Parkinson disease. Neurology 31: 19–23PubMedCrossRefGoogle Scholar
  6. Elsworth JD, Glover V, Reynolds GP, Sandler M, Lees AJ, Puapradit P, Shaw KM, Stern KM, Kumar P (1978) Deprenyl administration in man: a selective monoamine oxidase B inhibitor without the “cheese effect”. Psychopharmacology 57: 33–38PubMedCrossRefGoogle Scholar
  7. Feiner AE, Waldmeier PC (1979) Cumulative effects of irreversible MAO inhibitors in vivo. Biochem Pharmacol 28: 995–1002CrossRefGoogle Scholar
  8. Fowler CJ, Tipton KF (1984) On the substrate specificities of the two forms of monoamine oxidase. J Pharm Pharmacol 36: 111–115PubMedCrossRefGoogle Scholar
  9. Fowler CJ, Oreland L, Marcusson J, Winblad B (1980) Titration of human brain monoamine oxidase-A and-B by clorgyline and L-deprenyl. Naunyn Schmiedebergs Arch Pharmacol 311: 263–272PubMedCrossRefGoogle Scholar
  10. Fowler CJ, Mantle TJ, Tipton KF (1982) The nature of the inhibition of rat liver monoamine oxidase types A and B by the acetylenic inhibitors clorgyline, l-deprenyl and pargyline. Biochem Pharmacol 31: 3555–3561PubMedCrossRefGoogle Scholar
  11. Fuentes JA, Neff NH (1975) Selective monoamine oxidase inhibitor drugs as aids in evaluating the role of type A and B enzymes. Neuropharmacology 14: 819–825PubMedCrossRefGoogle Scholar
  12. Garrick NA, Scheinin M, Chang WH, Linnoila M, Murphy DL (1984) Differential effects of clorgyline on catecholamine and indoleamine metabolites in the cerebrospinal fluid of rhesus monkeys. Biochem Pharmacol 33: 1423–1427PubMedCrossRefGoogle Scholar
  13. Hsu YP, Powell JF, Sims KB, Breakefield XO (1989) Molecular genetics of the monoamine oxidases. J Neurochem 53: 12–18PubMedCrossRefGoogle Scholar
  14. Johnston JP (1968) Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol 17: 1285–1297PubMedCrossRefGoogle Scholar
  15. Karoum DF, Wyatt RJ (1982) Metabolism of (-)deprenyl’s therapeutic benefit: a biochemical assessment. Neurology 32: 503–509PubMedCrossRefGoogle Scholar
  16. Karoum F, Neff NH (1982) Quantitative gas chromatography-mass spectrometry (GC-MS) of biogenic amines. In: Spector S, Back N (eds) Theory and practice. Alan R Liss, New York, pp 39–54 (Modern Methods in Pharmacology)Google Scholar
  17. Karoum F, Nasrallah H, Potkin S, Chuang L, Moyer-Schwing J, Phillips I, Wyatt RJ (1979) Mass fragmentography of phenylethylamine m-and p-tyramine, and related amines in plasma cerebrospinal fluid, urine, and brain. J Neurochem 33: 201–212PubMedCrossRefGoogle Scholar
  18. Karoum F, Potkin SG, Murphy DL, Wyatt RJ (1980) Quantiation and metabolism of phenylethylamine and tyramine’s three isomers in humnas. In: Mosnaim AD, Wolf ME (eds) Noncatecholic phenylethylamines. Marcel Dekker, New York, pp 177–191Google Scholar
  19. Karoum F, Torrey EF, Murphy DL, Wyatt RJ (1985) The origin, drug interaction, urine, plasma and CSF concentrations of phenylacetic acid in normal and psychiatric subjects. In: Boulton AA, Baker GB, Dewhurst WG, Sandler M (eds) Neurobiology of the trace amine. Humana Press, Clifton NJ, pp 457–473Google Scholar
  20. Lenders JWM, Eisenhofer G, Abeling NGGM, Berger W, Murphy DL, Konings CH, Wagemarkers LMB, Kopin IJ, Karoum F, van Gennip AH, Brunner HG (1996) Specific genetic deficiencies of the A and B isoenzymes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes. J Clin Invest 97: 1–10CrossRefGoogle Scholar
  21. Liebowitz MR, Karoum Q FM, Davies SO, Schwartz D, Levitt M, Linnoila M (1985) Biochemical effects of L-deprenyl in atypical depressives. Biol Psychiatry 20: 558–565PubMedCrossRefGoogle Scholar
  22. Linnoila M, Karoum F, Potter WZ (1982) Effect of low-dose clorgyline on 24-hour urinary monoamine excretion in patients with rapidly cycling bipolar affective disorder. Arch Gen Psychiatry 39: 513–516PubMedCrossRefGoogle Scholar
  23. Lipper S, Murphy DL, Slater S, Buchsbaum MS (1979) Comparative behavioral effects of clorgyline and pargyline in man: a preliminary evaluation. Psychopharmacology 62: 123–128PubMedCrossRefGoogle Scholar
  24. Major LF, Murphy DL, Lipper S, Gordon E (1979) Effects of clorgyline and pargyline on deaminated metabolites of norepinephrine, dopamine and serotonin in human cerebrospinal fluid. J Neurochem 32: 229–231PubMedCrossRefGoogle Scholar
  25. Mann JJ, Aarons SF, Wilner PJ, Keilp JG, Sweeney JA, Pearlstein T, Frances AJ, Kocsis JH, Brown RP (1989) A controlled study of the antidepressant efficacy and side effects of (—)-deprenyl: a selective monoamine oxidase inhibitor. Arch Gen Psychiatry 46: 45–50PubMedCrossRefGoogle Scholar
  26. McKenna KF, Baker GB, Coutts RT (1993) Urinary excretion of bioactive amines and their metabolites in psychiatric patients receiving phenelzine. Neurochem Res 18: 1023–1027PubMedCrossRefGoogle Scholar
  27. Murphy DL (1978) Substrate-selective monoamine oxidases: inhibitor, tissue, species and functional differences. Biochem Pharmacol 27: 1889–1893PubMedCrossRefGoogle Scholar
  28. Murphy DL, Lipper S, Slater S, Shiling D (1979) Selectivity of clorgyline and pargyline as inhibitors of monoamine oxidases A and B in vivo in man. Psychopharmacology 62: 129–132PubMedCrossRefGoogle Scholar
  29. Murphy DL, Pickar D, Jimerson D, Cohen RM, Garrick NA, Karoum F, Wyatt RJ (1981) Biochemical indices of the effects of the selective MAO inhibitors clorgyline, pargyline and deprenyl in man. In: Usdin E, Dahl SG, Gram LF, Lingjaerde O (eds) Clinical pharmacology in psychiatry: neuroleptic and antidepressant research. Macmillan, London, pp 307–316Google Scholar
  30. Murphy DL, Garrick NA, Cohen RM (1983) Monoamine oxidase inhibitors and monoamine oxidase: biochemical and physiological aspects relevant to human psychopharmacology. In: Burrows JD, Norman TR, Davies E (eds) Drugs in psychiatry. Antidepressants. Elsevier Press, Amsterdam, pp 209–227Google Scholar
  31. Murphy DL, Garrick NA, Aulakh CS, Cohen RM (1984a) New contributions from basic science to understanding the effects of monoamine oxidase inhibiting antidepressants. J Clin Psychiatry 45: 37–43PubMedGoogle Scholar
  32. Murphy DL, Karoum F, Alterman I, Lipper S, Wyatt RJ (1984b) Phenylethylamine, tyramine and other trace amines in patients with affective disorders: associations with clinical state and antidepressant drug treatment. In: Boulton AA, Baker GB, Dewhurst WG, Sandler M (eds) Neurobiology of the trace amines. Humana Press, Clifton NJ, pp 449–514Google Scholar
  33. Murphy DT, Sunderland T, Cohen RM (1984c) Monoamine oxidase-inhibiting antidepressants: a clinical update. Psychiatr Clin North Am 7: 549–562PubMedGoogle Scholar
  34. Murphy DL, Aulakh CS, Garrick NA, Sunderland T (1987) Monoamine oxidase inhibitors as antidepressants: implications for the mechanism of action of antidepressants and the psychobiology of the affective disorders and some related disorders. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 545–552Google Scholar
  35. Murphy DL, Sims KB, Karoum F, de la Chapelle A, Norio R, Sankila E-M, Breakefield XO (1990) Marked amine and amine metabolite changes in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase. J Neurochem 54: 242–247PubMedCrossRefGoogle Scholar
  36. Murphy DL, Sims KB, Karoum F, Garrick NA, de la Chapelle A, Sankila EM, Norio R, Breakefield XO (1991) Plasma amine oxidase activities in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase. J Neural Transm [Gen Sect] 83: 1–12CrossRefGoogle Scholar
  37. Owen F, Cross AJ, Lofthouse R, Glover V (1979) Distribution and inhibition characteristics of human brain monoamine oxidase. Biochem Pharmacol 28: 1077–1080PubMedCrossRefGoogle Scholar
  38. Potter WZ, Murphy DL, Wehr TA, Linnoila M, Goodwin FK (1982) Clorgyline. A new treatment for patients with refractory rapid-cycling disorder. Arch Gen Psychiatry 39: 505–510PubMedCrossRefGoogle Scholar
  39. Potter WZ, Scheinin M, Golden RN, Rudorfer MV, Cowdry RW, Calil HM, Ross RJ, Linnoila M (1985) Selective antidepressants and cerebrospinal fluid. Arch Gen Psychiatry 42: 1171–1177PubMedCrossRefGoogle Scholar
  40. Quitkin FM, Liebowitz MR, Stewart JW, McGrath PJ, Harrison W, Rabkin JG, Markowitz J, Davies SO (1984) L-Deprenyl in atypical depressives. Arch Gen Psychiatry 41: 777–781PubMedCrossRefGoogle Scholar
  41. Sims KB, de la Chapelle A, Norio R, Sankila E-M, Hsu Y-PP, Rinehart WB, Corey TJ, Ozelius L, Powell JF, Bruns G, Gusella JF, Murphy DL, Breakefield XO (1989) Monoamine oxidase deficiency in males with an X chromosome deletion. Neuron 2: 1069–1076PubMedCrossRefGoogle Scholar
  42. Sunderland T, Mueller EA, Cohen RM, Jimerson DC, Pickar D, Murphy DL (1985) Tyramine pressor sensitivity changes during deprenyl treatment. Psychopharmacology 86: 432–437PubMedCrossRefGoogle Scholar
  43. Sunderland T, Cohen RM, Molchan S, Lawlor BA, Mellow AM, Newhouse PA, Tariot PN, Mueller EA, Murphy DL (1994) High dose selegiline in treatment-resistant older depressives. Arch Gen Psychiatry 51: 607–615PubMedCrossRefGoogle Scholar
  44. Weyler W, Hsu Y-P, Breakefield XO (1990) Biochemistry and genetics of monoamine oxidase. Pharmacol Ther 47: 391–417PubMedCrossRefGoogle Scholar
  45. Zametkin A, Rapoport JL, Murphy DL, Linnoila M, Karoum F, Potter WZ, Ismond D (1985) Treatment of hyperactive children with monoamine oxidase inhibitors. II. Plasma and urinary monoamine findings after treatment. Arch Gen Psychiatry 42: 969–973PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • D. L. Murphy
    • 1
    • 8
  • F. Karoum
    • 2
  • D. Pickar
    • 3
  • R. M. Cohen
    • 4
  • S. Lipper
    • 5
  • A. M. Mellow
    • 6
  • P. N. Tariot
    • 7
  • T. Sunderland
    • 1
  1. 1.Laboratory of Clinical ScienceNational Institute of Mental HealthBethesdaUSA
  2. 2.Neuroscience Center, St. Elizabeth’s HospitalNational Institute of Mental HealthUSA
  3. 3.Experimental Therapeutics BranchNational Institute of Mental HealthBethesdaUSA
  4. 4.Laboratory of Cerebral MetabolismNational Institute of Mental HealthBethesdaUSA
  5. 5.Department of PsychiatryDuke University School of MedicineDurhamUSA
  6. 6.Department of PsychiatryUniversity of Michigan School of MedicineAnn ArborUSA
  7. 7.Department of PsychiatryUniversity of Rochester Medical CenterRochesterUSA
  8. 8.Laboratory of Clinical ScienceNIMH, NIH Clinical Center, 10-3D41BethesdaUSA

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