Neurochemical Research

, Volume 18, Issue 9, pp 1023–1027 | Cite as

Urinary excretion of bioactive amines and their metabolites in psychiatric patients receiving phenelzine

  • K. F. McKenna
  • G. B. Baker
  • R. T. Coutts
Original Articles


Phenelzine [2-phenylethylhydrazine] (PLZ), a potent inhibitor of monoamine oxidase (MAO)-A and-B, is used widely in psychiatry. We have studied the effects of PLZ administration on urinary excretion of several bioactive amines and their metabolites in psychiatric patients. Urine samples (24-hour) were collected prior to treatment and again at 2 and 4 weeks of treatment with PLZ (30–90 mg daily in divided doses). Amines and metabolites analyzed included 2-phenylethylamine (PEA), m-and p-tyramine (m-and p-TA), phenylacetic acid (PAA), m-and p-hydroxyphenylacetic acid (m-and p-OH-PAA), tryptamine (T), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), normetanephrine (NME), 3-methoxy-4-hydroxyphenylglycol (MHPG), 3-methoxytyramine (3-MT), and homovanillic acid (HVA). Levels of PEA, p-TA, 5-HT, and T were elevated during treatment with PLZ, but no significant changes in urinary excretion of the acid metabolites PAA, p-OH-PAA, and 5-HIAA were observed. Urinary levels of the noradrenaline metabolites NME and MHPG were increased and decreased, respectively; a similar pattern was observed with the dopamine metabolites 3-MT and HVA. There was an elevation in levels of m-TA and a decrease in its acid metabolite m-OH-PAA during the treatment with PLZ.

Key Words

Phenelzine monoamine oxidase bioactive amines humans urinary excretion 


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  1. 1.
    Philips, S. R., and Boulton, A. A. 1979. The effect of monoamine oxidase inhibitors on some arylalkylamines in rat striatum. J. Neurochem. 33:159–167.PubMedGoogle Scholar
  2. 2.
    Philips, S. R., Baker, G. B., and McKim, H. R. 1980. Effects of tranylcypromine on the concentrations of some trace amines in the diencephalon and hippocampus of the rat. Experientia 36:241–242.PubMedGoogle Scholar
  3. 3.
    Baker, G. B., Greenshaw, A. J., and Coutts, R. T. 1988. Chronic adminstration of MAO inhibitors: implications for interactions between trace amines and catecholamines. Pages 569–572in Dahlstrom, A., Belmaker, R. H., and Sandler, M. (eds.), Progress in Catecholamine Research, Part A: Basic Aspects and Peripheral Mechanisms, Alan R. Liss, New York, N.Y.Google Scholar
  4. 4.
    Baker, G. B., Martin, I. L., and Mitchell, P. R. 1977. The effects of some indolalkylamines on the uptake and release of 5-hydroxytryptamine in rat striatum. Br. J. Pharmacol. 61:151P-152P.PubMedGoogle Scholar
  5. 5.
    Raiteri, M., del Carmine, R., Bertollini, A., and Levi, G. 1977. Effects of sympathomimetic amines on the synaptosomal transport of noradrenaline, dopamine and 5-hydroxytryptamine. Eur. J. Pharmacol. 41:133–143.PubMedGoogle Scholar
  6. 6.
    Jones, R. S. G., and Boulton, A. A. 1981. Tryptamine and 5-hydroxytryptamine's actions and interactions on cortical neurones in the rat. Life Sci 27:1849–1856.Google Scholar
  7. 7.
    Paterson, I. A., Juorio, A. V., and Boulton, A. A. 1990. 2-Phenylethylamine: a modulator of catecholamine transmission in the mammalian central nervous system? J. Neurochem. 55:1827–1837.PubMedGoogle Scholar
  8. 8.
    Boulton, A. A. 1985. The trace amines: recent overview and future pointers. Pages 3–12,in Boulton, A.A., Bieck, P.R., Maitre, L., and Riederer, P. (eds.), Neuropsychopharmacology of the Trace Amines, Humana Press, Clifton, N.J.Google Scholar
  9. 9.
    Vaccari, A. 1988. High affinity binding of p-tyramine: a process in search of a function. Pages 119–132, in Boulton, A. A., Jourio, A. V., and Downer, R. G. H. (eds.), Trace, Amines: Comparative and Clinical Neurobiology, Humana Press, Clifton, N.J.Google Scholar
  10. 10.
    Dewhurst, W. G. 1968. New theory of cerebral amine function and its clinical application. Nature (Lond.) 218:1130–1133.Google Scholar
  11. 11.
    Murphy, D. L., Brand, E., Goldman, T., Baker, M., Wright, C., van Kammen, D., and Gordon, E. 1977. Platelet and plasma amine oxidase inhibition and urinary amine excretion changes during phenelzine treatment. J. Nerv. Ment. Dis. 164:129–134.PubMedGoogle Scholar
  12. 12.
    Bieck, P. R., Nilsson, E., Schick, C., Waldmeier, P. C., and Lauber, J. 1984. Urmary excretion of tryptamine in comparison to normetanephrine and β-phenylethylamine in human volunteers after subchronic treatment with different monoamine oxidase inhibitors. Pages 525–539 in Boulton, A. A., Baker, G. B., Dewhurst, W. G., and Sandler, M. (eds.), Neurobiology of the Trace Amines, Humana Press, Clifton, N.J.Google Scholar
  13. 13.
    Baker, G. B., Coutts, R. T., Yeung, J. M., Hampson, D. R., McIntosh, G. J. A., and McIntosh, M. G. 1985. Chronic administration of monoamine oxidase inhibitors: basic and clinical investigations. Pages 317–328 in Boulton, A. A., Maitre, L., Bieck, P. R., and Riederer, P. (eds.), Neuropsychopharmacology of the Trace Amines, Humana Press, Clifton, N.J.Google Scholar
  14. 14.
    Liebowitz, M. R., Karoum, F., Quitkin, F. M., Davies, S. O., Schwartz, D., Levitt, M., and Linnoila, M. 1985. Biochemical effects of L-deprenyl in atypical depressives. Biol. Psychiat. 20:558–565.PubMedGoogle Scholar
  15. 15.
    Tollefson, G. D. 1983. Monoamine oxidase inhibitors: a review. J. Clin. Psychiat. 44:280–288.Google Scholar
  16. 16.
    Murphy, D. L., Aulakh, D. S., Garrick, N. A., and 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. Pages 545–552 in Meltzer, H. Y. (ed.) Psychopharmacology: The Third Generation of Progress, Raven Press, New York, N.Y.Google Scholar
  17. 17.
    Baker, G. B., LeGatt, D. F., and Coutts, R. T. 1982. Effects of acute and chronic administration of phenelzine on 2-phenylethylamine levels in rat brain. Proc. West. Pharmacol. Sco. 25:417–420.Google Scholar
  18. 18.
    Dyck, L. E., Durden, D. A., and Boulton, A. A. 1985. Formation of β-phenylethylamine from the antidepressant, β-phenylethylhydrazine. Biochem. Pharmacol. 34:1925–1929.Google Scholar
  19. 19.
    Clineschmidt, B. V., and Horita, A. 1969. The monoamine oxidase catalyzed degration of phenelzine-1-14C, an irreversible inhibitor of monoamine oxidase—I. Studies in vitro. Biochem. Pharmacol. 18:1011–1020.PubMedGoogle Scholar
  20. 20.
    Clineschmidt, B. V., and Horita, A. 1969. The monoamine oxidase catalyzed degration of phenelzine-1-14C, an, irreversible inihibitor of monoamine oxidase—II. Studies in vivo. Biochem. Pharmacol. 18:1021–1028.PubMedGoogle Scholar
  21. 21.
    Robinson, D. S., Cooper, T. B., Jindal, S. P., Corcella, J., and Lutz, T. 1985. Metabolism and pharmacokinetics of phenelzine: lack of evidence for acetylation pathway in humans. J. Clin. Psychopharmacol. 5:333–337.PubMedGoogle Scholar
  22. 22.
    McKenna, K. F., Baker, G. B., Coutts, R. T., Rauw, G., Mozayani, A., and Danielson, J. T. 1990. Recent studies on the MAO inhibitor phenelzine and its possible metabolites. J. Neural Transm. 32(Suppl):113–118.Google Scholar
  23. 23.
    Mallinger, A. G., and Smith, E. 1991. Pharmacokinetics of monoamine oxidase inhibitors. Psychopharmacol. Bull. 27:493–502.PubMedGoogle Scholar
  24. 24.
    McKenna, K. F. and Baker, G. B. 1993. Pharmacologie des IMAO et utilisation des IMAO irréversibles dans la dépression. Pages 86– Bourin, M. (ed.) Les I.M.A.O., Editions Ellipses, Pariis, France.Google Scholar
  25. 25.
    Baker, G. B., Rao, T. S., and Coutts, R. T. 1986. Electroncapture gas chromatographic analysis of β-phenylethylamine in tissues and body fluids using pentafluorobenzenesulfonyl chloride for derivatization. J. Chromatogr. Biomed. Appl. 381:211–217.Google Scholar
  26. 26.
    Wong, J. T. F., Baker, G. B., and Coutts, R. T. 1988. Rapid and simple procedure for the determination of urinary phenylacetic acid using derivatization in aqueous medium followed by electroncapture gas chromatography. J. Chromatog. Biomed. Applic. 428:140–146.Google Scholar
  27. 27.
    Baker, G. B., Yeragani, V. K., Dewhurst, W. G., Coutts, R. T., MacDonald, R. N., and Wong, J. T. F. 1987. Simultaneous analysis of urinary m-and p-hydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindole-3-acetic acid using electron-capture gas chromatography. Biochem. Arch. 3:257–264.Google Scholar
  28. 28.
    Coutts, R. T., Baker, G. B., LeGatt, D. F., McIntosh, G. J., Hopkinson, G., and Dewhurst, W. G. 1981. Screening for amines of psychiatric interest in urine using gas chromatography with electron-capture detection. Prog. Neuro-Psychopharmacol. 5:565–568.Google Scholar
  29. 29.
    Baker, G. B., Coutts, R. T., Bornstein, R. A., Dewhurst, W. G., Douglass, A. B., and MacDonald, R. M. 1987. An electroncapture gas chromatographic method for analysis of urinary 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG). Res. Commun. Chem. Path. Pharmacol. 54:141–144.Google Scholar
  30. 30.
    Antonin, K. H., Nilsson, E., Waldmeier, P. C., and Bieck, P. R. 1985. Urinary excretion of tryptamine, MHPG, HVA, VMA and HIAA by volunteers treated with CGP 4718A, a combined inhibitor of MAO-A and 5-HT uptake. Pages 453–460 in Boulton, A. A., Maitre, L., Bieck, P. R., and Riederer, P. (eds.), Neuropsychopharmacology of the Trace Amines, Humana Press, Clifton, N.J.Google Scholar
  31. 31.
    Tipton, K. F., and Spires, I. P. C. 1972. Oxidation of 2-phenylethylhydrazine by monoamine oxidase. Biochem. Pharmacol. 21:268–270.PubMedGoogle Scholar
  32. 32.
    Boulton, A. A., Dyck, L. E., and Durden, D. A. 1975. Hydroxylation of β-phenylethylamine in the rat. Life Sci. 15:1673–1683.Google Scholar
  33. 33.
    Callaghan, O., Mosnaim, A., Chevesch, J., and Wolf, M. E. 1984. The kinetics of hydroxylation of phenylethylamine, amphetamine and phenylalanine in rodent tissues. Pages 307–312 in Boulton, A. A., Baker, G. B., Dewhurst, W. G., and Sandler, M., (eds.), Neurobiology of the Trace Amines, Humana Press, Clifton, N.J.Google Scholar
  34. 34.
    McKenna, K. F., Yu. P. H., Davis, B. A., Baker, G. B., and Coutts, R. T. 1991. Urinary excretion of bioactive amines in psychiatric patients treated with phenelzine. Proc. 14th Ann. Meet. Can. Coll. Neuropsychopharmacol., Hamilton, Ontario, p. 48.Google Scholar
  35. 35.
    Karoum, F., Torry, E. F., and Murphy, D. L. 1984. The origin, drug interaction, urine, plasma and CSF concentrations of phenylacetic acid in normal and psychiatric subjects. Pages 457–473 in Boulton, A. A., Baker, G. B., Dewhurst, W. G., and Sandler, M., (eds.), Neurobiology of the Trace Amines, Humana Press, Clifton, N.J.Google Scholar
  36. 36.
    Karoum, F., Potkin, S. D., Chuang, L. W., Murphy, D. L., Liebowitz, M. R., and Wyatt, R. J. 1984. Phenylacetic acid excretion in schizophrenia and depression: the origins of PAA in man. Biol. Psychiat. 19:546–550.Google Scholar
  37. 37.
    Baker, G. B., Bieck, P., Antonin, K. H., Schick, C. and van Muyden, J. 1989. Urinary excretion of β-phenylethylamine and phenylacetic acid in volunteer subjects treated with phenelzine. J. Neurochem. 52:S 155.Google Scholar

Copyright information

© Plenum Publishing Corporation 1993

Authors and Affiliations

  • K. F. McKenna
    • 1
  • G. B. Baker
    • 1
  • R. T. Coutts
    • 1
  1. 1.Neurochemical Research Unit, Department of PsychiatryUniversity of AlbertaEdmontonCanada

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