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Metabolism of alpha-methyltyrosine in man: relationship to its potency as an inhibitor of catecholamine biosynthesis.

Authors
  • Engelman, K
  • Jéquier, E
  • Udenfriend, S
  • Sjoerdsma, A
Type
Published Article
Journal
The Journal of clinical investigation
Publication Date
Mar 01, 1968
Volume
47
Issue
3
Pages
568–576
Identifiers
PMID: 5637144
Source
Medline
License
Unknown

Abstract

The metabolic fate of the tyrosine hydroxylase inhibitor, alpha-methyl-para-tyrosine (alpha-MPT), was studied after oral administration of single and multiple doses to patients with pheochromocytoma and essential hypertension. No major urinary excretion product was found other than the drug itself, which accounted for 44-88% of the fate of single or repeated oral doses. Though less than 1% of the administered drug could be recovered in the urine as catechol metabolites, it was possible to identify alpha-methyldopa, alpha-methyldopamine, and alpha-methylnorepinephrine and to quantify the excretion of the first two of these compounds. This minor route of metabolism required revision of methodology (presented herein) for measuring urinary catecholamines during alpha-MPT treatment since these compounds produce spurious fluorescence in routine methods of assay for catecholamines. The catechol metabolites probably are not present in sufficient amounts to contribute to the biochemical effects of the drug. Determination of plasma concentrations of alpha-MPT during maintenance therapy and considerations of the kinetics of enzyme inhibition enabled a calculation to be made of the degree of inhibition of catecholamine synthesis to be expected in the patient. This was calculated to be about 75% for the highest doses employed and is similar in magnitude to experimentally determined values.

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