Urinary Excretion of Tryptamine in Comparison to Normetanephrine and Beta-Phenylethylamine in Human Volunteers After Subchronic Treatment with Different Monoamine Oxidase Inhibitors

  • P. R. Bieck
  • E. Nilsson
  • C. Schick
  • P. C. Waldmeier
  • J. Lauber

Abstract

Measurement of urinary tryptamine excretion has been used extensively in the past as indicator for monoamine oxidase (MAO) inhibition in man. Basal tryptamine excretion (ug/g creatinine) differs between sexes (p< 0.001). The values obtained (x ± SD) were: 66 ± 26 in 13 males (n = 90) and 112 ± 42 in 9 females (n = 60). The higher basal tryptamine excretion and the larger tryptamine/indole acetic acid ratios in females, together with the greater effect of MAO inhibitors suggest a lower basal MAO-A activity in women. Different hormonal influences could explain the large interindividual and intraindividual seasonal variation of tryptamine excretion in females. By comparison of urinary tryptamine, normetanephrine and beta-phenylethylamine during subchronic treatment with three different MAO inhibitors it could be shown that tryptamine is a MAO-A substrate. MAO-A inhibition by the new reversible selective inhibitor CGP 11 305 A (150mg/d) caused parallel increases of tryptamine (320%) and normetanephrine (360%), but did not change urinary phenylethylamine. Selective MAO-B inhibition with deprenyl (10mg/d) enhanced phenylethylamine excretion (2600%), but did not affect tryptamine. During treatment with tranylcypromine (20mg/d), the unspecific inhibitor of both MAO-A+B, all three metabolites increased significantly (between 440% and 720%).

Keywords

Placebo Creatinine Tryptophan Oestradiol Indole 

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References

  1. Baker, G. B., Calverley, D. G., Dewhurst, W. G. and Martin I. L. (1979) A sensitive gas chromatographic technique for quantification of urinary tryptamine. Br. J. Pharmacol. 67, 469 P.Google Scholar
  2. Bieck, P. R. and Antonin, K. H. (1932) Monoamine oxidase inhibition by tranylcypromine: assessment in human volunteers. Eur. J. Clin. Pharmacology 22, 301–308.CrossRefGoogle Scholar
  3. Bieck, P., Antonin, K.H., and Jedrychowski, M. (1983) Monoamine oxidase inhibition in healthy volunteers by CGP 11 305 A, a new specific inhibitor of MAO-A. Mod. Probl. Pharmacopsychiat. 19, 53–62.Google Scholar
  4. Cremer, G., Antonin, K. H. and Bieck, P. (1983) Monoamine oxidase inhibition in healthy volunteers by (-)deprenyl (D). Naunyn-Schmiedeberg’s Arch. Pharmacol. 322, Suppl. R 132.Google Scholar
  5. Elsworth, J. D. (1978) Deprenyl andministration in man: A selective monoamine oxidase B inhibitor without the “cheese effect”. Psychopharmacology 57, 33–38.PubMedCrossRefGoogle Scholar
  6. Fowler, C. J., Callingham, B. A., Mantle, T. J. and Tipton, K. F. (1978) Monoamine oxidase A and B: a useful concept? Biochem. Pharmacol. 27, 97–101.CrossRefGoogle Scholar
  7. Fuller, R. W. and Roush, B. W. (1972) Substrate- selective and tissue selective inhibition of monoamine oxidase. Arch. Int. Pharmacodyn. Ther. 198, 270–276.PubMedGoogle Scholar
  8. Holzbauer, M. and Youdim, M. B. H. (1973 ) The oestrus cycle and monoamine oxidase activity. Br. J. Pharmacol. 48, 600–608.PubMedGoogle Scholar
  9. Houslay, M. D. and Tipton, K. F. (1974) A kinetic evaluation of monoamine oxidase activity in rat liver mitrochondrial outer membranes. Biochem. J. 139, 645–652.PubMedGoogle Scholar
  10. LaBrosse, E. H., Kopin, I. J., Felix Jr., W. R. and Westlake, R. J. (1964) Urinary tryptamine and indole-3-acetic acid excretion by schizophrenic patients: use of the tryptamine/in-dole acetic ratio as an index of monoamine oxidase inhibition. J. Psychiat. Res. 2, 185–197.CrossRefGoogle Scholar
  11. Lauber, J. and Waldmeier, P. C. (1983) In preparation. Biol. Med. 109, 225–227.Google Scholar
  12. Levine, R. J and Sjoerdsma, A. (1962) Monoamine oxidase activity in human tissues and intestinal biopsy specimens. Proc. Soc. Exp. Biol. Med. 109, 225–227.PubMedGoogle Scholar
  13. Linnoila, M., Karoum, F., Potter, W. Z. (1982) Effect of low-dose clorgyline on 24-hour urinary monoamine excretion in patients with rapidly cycling bipolar affective disorder. Arch. Gen. Psychiatry. 39 513–516.PubMedGoogle Scholar
  14. Luine, V. N. and McEwen, B. S. (1977) Effect of oestradiol on turnover of type A monoamine oxidase in brain. J. Neurochem. 28, 1221–1226.PubMedCrossRefGoogle Scholar
  15. Murphy, D. L., Cohen, R. M., Siever, L. J., Roy, B., Karoum, F., Uyatt, R. J., Garrick, N. A. and Linnoila, M. (1983) Clinical and laboratory studies with selective monoamine-oxidase-in- hibiting drugs. Mod. Probl. Pharmacopsychiat. 19, 287–303.Google Scholar
  16. Nilsson, E. and Hengen, N. (1983) Measurement of indole-3-acetic acid in human urine by HPLC-UV. In preparation.Google Scholar
  17. Nilsson, E. and Schick, Ch. (1983) Effect of different monoamine oxidase (MAO) inhibitors on human urinary tryptamine excretion. Naunyn-Schmiedeberg1s Arch. Pharmacol. 322, Suppl. R 133.Google Scholar
  18. Rodnight, R. (1961) Body fluid indoles in mental illness. Int. Rev. Neurobiol. 3, 251–292.CrossRefGoogle Scholar
  19. Sjoerdsma, A., Oates, J. A., Zaltzman, P., Udenfriend, S. (1959) Identification and assay of urinary tryptamine: application as an index of monoamine oxidase inhibition in man. J. Pharmacol. Exp. Ther. 126, 217–222.PubMedGoogle Scholar
  20. Waldmeier, P. C., Baumann, P. A., Delini-Stula, A., Bernasconi, R., Sigg, K., Buech, O., Felner, A. E. (1983a) Characterization of a new, short-acting and specific inhibitor of type A monoamine oxidase. Mod. Probl. Pharmacopsychiat. 19, 31–52.Google Scholar
  21. Waldmeier, P. C., Antonin, K. H., Feldtrauer, J. J. Grunenwald, Ch., Paul, E., Lauber, J. and Bieck, P. (1983b) Urinary excretion of o-methylated catecholamines, and phenylethylamine in human volunteers treated with tranylcypromine and CGP 11 305 A. Eur. J. Clin Pharmacology, in print.Google Scholar
  22. Weissbach, H., King, U., Sjoerdsma, A. and Udenfriend, S. (1959) Formation of indole-3- acetic acid and tryptamine in animals. J. Biol. Chem. 234, 81–86.PubMedGoogle Scholar
  23. White, H. L. and Tansik, R. L. (1979) Characterization of multiple substrate binding sites of MAO, in Monoamine oxidases: structure, function and altered functions ( Singer, Van Korff, Murphy, eds.) pp. 129–144. Academic Press, New York.Google Scholar
  24. Youdim, M. B. H. and Finberg, J. P. M. (1933) Monoamine oxidase inhibitor antidepressants, in Psychopharmacology Part I: Preclinical Psychopharmacology ( GrahameSmith, Cowen, eds.) pp. 38–70. Excerpta Medica, Amsterdam.Google Scholar

Copyright information

© The Humana Press Inc. 1984

Authors and Affiliations

  • P. R. Bieck
    • 1
  • E. Nilsson
    • 1
  • C. Schick
    • 1
  • P. C. Waldmeier
    • 2
  • J. Lauber
    • 2
  1. 1.Human Pharmacology InstituteCIBA-GEIGY GmbHFederal Republic of Germany
  2. 2.Research Department, Pharmaceuticals DivisionCIBA-GEIGY Ltd.BasleSwitzerland

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