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. 1968 Mar;47(3):577–594. doi: 10.1172/JCI105754

Biochemical and pharmacologic effects of α-methyltyrosine in man

Karl Engelman 1, David Horwitz 1, Eric Jéquier 1, Albert Sjoerdsma 1
PMCID: PMC297204  PMID: 5637145

Abstract

Alpha methyltyrosine (α-MPT) was administered to 52 patients from 4 days to 10 months; 22 patients were cases of pheochromocytoma and 20 had essential hypertension. Inhibition of catecholamine synthesis in the range of 50-80% was achieved with divided daily drug dosage of from 1.0 to 4.0 g. Striking clinical benefit was noted in patients with pheochromocytoma in whom the drug was used in preparation for surgery and during chronic medical management. The drug appeared to have limited usefulness when used in essential hypertension, unless added to existing therapy with conventional agents. No beneficial effects were noted in thyrotoxicosis, glaucoma, and Raynaud's phenomenon. Untoward effects in order of decreasing incidence were: sedation (with insomnia on withdrawal), anxiety, tremor, diarrhea, and galactorrhea. Drug crystalluria, which has been observed in animals and is currently restrictive of clinical trials, was not observed in these studies. Evidence is presented that the minor conversion of α-MPT to methyldopa probably does not contribute significantly to the central and peripheral effects of the drug.

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Selected References

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  1. CANARY J. J., SCHAAF M., DUFFY B. J., Jr, KYLE L. H. Effects of oral and intramuscular administration of reserpine in thyrotoxicosis. N Engl J Med. 1957 Sep 5;257(10):435–442. doi: 10.1056/NEJM195709052571001. [DOI] [PubMed] [Google Scholar]
  2. ENGELMAN K., MUELLER P. S., SJOERDSMA A. ELEVATED PLASMA FREE FATTY ACID CONCENTRATIONS IN PATIENTS WITH PHEOCHROMOCYTOMA. CHANGES WITH THERAPY AND CORRELATIONS WITH THE BASAL METABOLIC RATE. N Engl J Med. 1964 Apr 23;270:865–870. doi: 10.1056/NEJM196404232701702. [DOI] [PubMed] [Google Scholar]
  3. ENGELMAN K., SJOERDSMA A. CHRONIC MEDICAL THERAPY FOR PHEOCHROMOCYTOMA; A REPORT OF FOUR CASES. Ann Intern Med. 1964 Aug;61:229–241. doi: 10.7326/0003-4819-61-2-229. [DOI] [PubMed] [Google Scholar]
  4. Engelman K., Jéquier E., Udenfriend S., Sjoerdsma A. Metabolism of alpha-methyltyrosine in man: relationship to its potency as an inhibitor of catecholamine biosynthesis. J Clin Invest. 1968 Mar;47(3):568–576. doi: 10.1172/JCI105753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. GAFFNEY T. E., BRAUNWALD E., KAHLER R. L. Effects of guanethidine on tri-iodothyronine-induced hyperthyroidism in man. N Engl J Med. 1961 Jul 6;265:16–20. doi: 10.1056/NEJM196107062650104. [DOI] [PubMed] [Google Scholar]
  6. Gordon R., Reid J. V., Sjoerdsma A., Udenfriend S. Increased synthesis of norepinephrine in the rat heart on electrical stimulation of the stellate ganglia. Mol Pharmacol. 1966 Nov;2(6):610–613. [PubMed] [Google Scholar]
  7. Howitt G., Rowlands D. J. Beta-sympathetic blockade in hyperthyroidism. Lancet. 1966 Mar 19;1(7438):628–631. doi: 10.1016/s0140-6736(66)90825-7. [DOI] [PubMed] [Google Scholar]
  8. Moore K. E., Wright P. F., Bert J. K. Toxicologic studies with alpha-methyltyrosine, an inhibitor of tyrosine hydroxylase. J Pharmacol Exp Ther. 1967 Mar;155(3):506–515. [PubMed] [Google Scholar]
  9. OATES J. A., GILLESPIE L., UDENFRIEND S., SJOERDSMA A. Decarboxylase inhibition and blood pressure reduction by alpha-methyl-3,4-dihydroxy-DL-phenylalanine. Science. 1960 Jun 24;131(3417):1890–1891. doi: 10.1126/science.131.3417.1890. [DOI] [PubMed] [Google Scholar]
  10. PETTINGER W. A., HORWITZ D., SJOERDSMA A. Lactation due to methyldopa. Br Med J. 1963 Jun 1;1(5343):1460–1460. doi: 10.1136/bmj.1.5343.1460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. PETTINGER W., HORWITZ D., SPECTOR S., SJOERDSMA A. ENHANCEMENT BY METHYLDOPA OF TYRAMINE SENSITIVITY IN MAN. Nature. 1963 Dec 14;200:1107–1108. doi: 10.1038/2001107a0. [DOI] [PubMed] [Google Scholar]
  12. SCHNECKLOTH R. E., KURLAND G. S., FREEDBERG A. S. Effect of variation in thyroid function on the pressor response to norepinephrine in man. Metabolism. 1953 Nov;2(6):546–555. [PubMed] [Google Scholar]
  13. SPECTOR S., SJOERDSMA A., UDENFRIEND S. BLOCKADE OF ENDOGENOUS NOREPINEPHRINE SYNTHESIS BY ALPHA-METHYL-TYROSINE, AN INHIBITOR OF TYROSINE HYDROXYLASE. J Pharmacol Exp Ther. 1965 Jan;147:86–95. [PubMed] [Google Scholar]
  14. Sjoerdsma A., Engelman K., Spector S., Udenfriend S. Inhibition of catecholamine synthesis in man with alpha-methyl-tyrosine, an inhibitor of tyrosine hydroxylase. Lancet. 1965 Nov 27;2(7422):1092–1094. doi: 10.1016/s0140-6736(65)90062-0. [DOI] [PubMed] [Google Scholar]

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