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α-Methyl-p-Tyrosine: A Review of its Pharmacology and Clinical Use

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Summary

Synopsis

α-Methyl-p-tyrosine1,2 is an orally active inhibitor of catecholamine synthesis which inhibits the hydroxylation of tyrosine to dopa. At dosages of 600 to 3500mg daily it is effective in controlling the hypertensive episodes and symptoms of catecholamine excess in phaeochromocytoma during preparation for surgery. Limited published experience suggests that it is effective in controlling hypertension and symptoms in malignant phaeochromocytoma, but further long term experience is needed. Concomitant administration of phenoxybenzamine and propranolol may be desirable in some patients and treatment with phentolamine is usually necessary to control hypertension during manipulation of the tumour.

Pharmacology

α-Methyl-p-tyrosine is an inhibitor of catecholamine synthesis peripherally as well as centrally and achieves this by inhibiting the hydroxylation of tyrosine to form dopa. The inhibition of catecholamine synthesis is evidenced by the dose-related reduction of urinary catecholamines and their metabolites when the drug is given at daily dosages of up to 1500mg. There is a further reduction at higher dosages but the magnitude of the decrease is proportionally less as dosage increases.

α-Methyl-p-tyrosine usually decreases blood pressure in patients with phaeochromocytoma but does not consistently decrease blood pressure in patients with essential hypertension. As α-methyl-p-tyrosine treatment may interfere with standard methods of estimation of urinary catecholamines it is advisable to determine total catecholamines as well as hydroxymethoxymandelic acid3 and methylated catecholamines.

Pharmacokinetics

Oral α-methyl-p-tyrosine is well absorbed and absorption appears constant in each individual over a wide dosage range. The drug is largely excreted via the kidneys, but extrarenal elimination has not been studied. The drug is metabolised to only a limited extent.

Therapeutic Studies

Case reports on the clinical use of α-methyl-p-tyrosine in phaeochromocytoma indicate that the drug controls hypertension and symptoms of catecholamine excess in most patients during preparation for surgical removal of the tumour. In some cases the addition of α-methyl-p-tyrosine to phenoxybenzamine plus propranolol has resulted in adequate control of symptoms previously unresponsive to the adrenergic blocking regimen. The opportunity to study the relative merit of using α-methyl-p-tyrosine alone or combined with adrenergic blocking drugs has seldom arisen, but in a patient with bilateral phaeochromocytoma, the use of α-methyl-p-tyrosine plus adrenergic blocking drugs resulted in a smoother pre- and postoperative course than α-methyl-p-tyrosine alone.

Long term administration of α-methyl-p-tyrosine in malignant phaeochromocytoma is limited, but the data available suggest that the drug can adequately control symptoms for periods of many months. The question as to whether or not tolerance occasionally develops to the therapeutic effects of the drug in phaeochromocytoma has not been fully clarified.

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Authors and Affiliations

  1. Australasian Drug Information Services, P.O. Box 34-030, Birkenhead, Auckland 10, New Zealand

    R. N. Brogden, R. C. Heel, T. M. Speight & G. S. Avery

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  1. R. N. Brogden
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  2. R. C. Heel
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  3. T. M. Speight
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  4. G. S. Avery
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Additional information

Various sections of the manuscript reviewed by: W.E. Bagnall, Department of Geriatric Medicine, St James University Hospital, Leeds, England; S. Bergman, Department of Urology, Tulane University, New Orleans, USA; V. De Quattro, Hypertensive Service, University of Southern California, Los Angeles, USA; K. Engelman, Hypertension and Clinical Pharmacology Section, University of Pennsylvania, Philadelphia, USA; J.H. Hengstmann, Medizinische Klinik Paul-Ehrlich-Haus, Bonn, Germany; N.F. Jones, St Thomas’ Hospital, London, England

‘Demser’ Merck Sharp and Dohme.

‘Demser’ is the l-isomer; the d-isomer is inactive.

Also known as vanillylmandelic acid (VMA).

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Brogden, R.N., Heel, R.C., Speight, T.M. et al. α-Methyl-p-Tyrosine: A Review of its Pharmacology and Clinical Use. Drugs 21, 81–89 (1981). https://doi.org/10.2165/00003495-198121020-00001

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