Abstract
The relationship between changes in IV tyramine pressor sensitivity accompanying selective monoamine oxidase (MAO) inhibitor treatment and estimates of MAO-A and MAO-B inhibition in vivo were studied. Reductions in platelet MAO activity provided an index of MAO-B inhibition, while changes in plasma 3-methoxy-4-hydroxyphenethylene glycol (MHPG) were used as an hypothesized reflection of MAO-A inhibition. Chronic treatment with the MAO-A inhibitor clorgyline and the MAO-B inhibitor pargyline showed significant inhibition of the alternate MAO enzyme as well, although this crossover effect was greater for pargyline than clorgyline. The MAO-B inhibitor deprenyl appeared to maintain the greatest degree of MAO inhibition selectivity in vivo. Tyramine pressor sensitivity changes accompanying administration of the MAO inhibitors were highly correlated with decreases in plasma MHPG (r=0.92), supporting our previous data indicating the rank order of clorgyline > pargyline > deprenyl for enhancement of tyramine pressor sensitivity and, thus, suggesting that tyramin potentiation is primarily a function of MAO-A rather than MAO-B inhibition. Changes in plasma MHPG are suggested to provide a potentially useful clinical index of in vivo MAO-A inhibition.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Campbell IC, Murphy DL, Gallager DW, Tallman JF, Marshall EF (1979a) Neurotransmitter-related adaptation in the central nervous system following chronic monoamine oxidase inhibition. In: Singer TP Van Korff RW, Murphy DL (eds) Monoamine oxidase: Structure function and altered functions. Academic, New York, pp 517–530
Campbell IC, Robinson DS, Lovenberg W, Murphy DL (1979b) The effects of chronic regimes of clorgyline and pargyline on monoamine metabolism in the rat brain. J Neurochem 32:49–55
Donnelly CH, Murphy DL (1977) Substrate and inhibitor-related characteristics of human platelet monoamine oxidase. Biochem Pharmacol 26:853–858
Elsworth JD, Glower V, Reynolds GP, Sandler M, Lees AJ, Phuapradt P, Shaw KM, Stern GM, Kumar P (1978) Deprenyl administration in man: A selective monoamine oxidase B inhibitor without the “cheese effect”. Psychopharmacology 57:33–38
Fuentes JA, Neff NH (1975) Selective monoamine oxidase inhibitor drugs as aids in evaluating the role of type-A and B enzymes. Neuropharmacology 14:819–825
Goridis C, Neff NH (1971) Monoamine oxidase in sympathetic nerves: A transmitter-specific enzyme type. Br J Pharmacol 43:814–818
Horwitz D, Lovenberg W, Engleman K, Sjoerdsma J (1964) Monoamine oxidase inhibitors, tyramine and cheese. JAMA 190:1108–1110
Jarrot B (1971) Occurrence and properties of monoamine oxidase in adrenergic neurons. J Neurochem 18:7–16
Knoll J (1979) Structure-activity relationships of the selective inhibitors of MAO-B. In: Singer TP, Van Korff RW, Murphy DL (eds) Monoamine oxidase: Structure, function and altered functions. Academic, New York, pp 431–446
Kopin IJ (1966) Biochemical aspects of release of norepinephrine and other amines from sympathetic nerve endings. Pharmacol Rev 18:784–792
Kopin IJ, Gordon EF (1962) Metabolism of 3H-norepinephrine released by tyramine and reserpine. J Pharmacol Exp Ther 138:351–359
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 32:229–231
Murphy DL (1978) Substrate-selective monoamine oxidases: Inhibitors, tissue species and functional differences. Biochem Pharmacol 27:1889–1893
Murphy DL, Brand E, Goldman T, Baker M, Wright C, van Kammen D, Gordon E (1977) Platelet and plasma oxidase inhibition and urinary amine excretion changes during phenelzine treatment. J Nerv Ment Dis 164:129–134
Murphy DL, Lipper S, Slater S, Shilling S (1979) Selectivity of clorgyline and pargyline as inhibitors of monoamine oxidases A and B in vivo in man. Psychopharmacology 62:129–132
Murphy DL, Wright C, Buchsbaum M, Costa J, Nichols A, Wyatt R (1976) Platelet and plasma amine oxidase activities in 650 normals: Sex and age differences and stability over time. Biochem Med 16: 254–265
Pickar D, Cohen RM, Jimerson DC, Murphy DL (1981) Tyramine infusions and selective MAO inhibitor treatment. I. Changes in pressor sensitivity. Psychopharmacology 74:4–7
Robinson DS, Nies A, Ravaris CL, Ives JO, Bartlett D (1978a) Clinical pharmacology of phenelzine. Arch Gen Psychiatry 35:629–635
Robinson DS, Nies A, Ravaris CL, Ives JO, Bartlett D (1978b) Clinical pharmacology of phenelzine: MAO activity and clinical response. In: Lipton MA, DiMascio A, Killam KF (eds) Psychopharmacology: A generation of progress. Raven, New York, pp 961–974
Takahashi S, Godse DD, Warsh JJ, Stancer HC (1977) A gas chromatographic-mass spectrometric (GC-MS) assay for 3-methoxy-4-hydroxy phenethyleneglycol and vanilmandelic acid in human serum. Clin Chim Acta 81:183–192
White HL, Tansik RL (1979) Characterization of multiple substrate binding sites of MAO. In: Singer TP, Van Korff RW, Murphy DL (eds) Monoamine oxidase: Structure, function and altered functions. Academic, New York, pp 129–144
Author information
Authors and Affiliations
Additional information
Presently with the Biological Psychiatry Branch, NIMH
Rights and permissions
About this article
Cite this article
Pickar, D., Cohen, R.M., Jimerson, D.C. et al. Tyramine infusions and selective monoamine oxidase inhibitor treatment. Psychopharmacology 74, 8–12 (1981). https://doi.org/10.1007/BF00431748
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00431748