Alternative catecholamine pathways after tyrosine hydroxylase inhibition in malignant pheochromocytoma.

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Kuchel O, Buu NT, Edwards DJ

Alternative catecholamine pathways after tyrosine hydroxylase inhibition in malignant pheochromocytoma.

J Lab Clin Med. 1990 Apr;115(4):449-53.

PubMed ID

1969915 [ View in PubMed

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Abstract

A suppression of norepinephrine, epinephrine, and its metabolites in malignant pheochromocytoma by metyrosine was associated with an increase in tyrosine, plasma DOPA, and sulfate esters of DOPA and dopamine, followed, with continuing metyrosine administration, by a further rise of both DOPA sulfate and dopamine sulfate. Urinary dopamine progressively increased in the course of metyrosine treatment, and this, along with the increase of the dopamine metabolite, dihydroxyphenylethanol, and plasma dopamine sulfate, occurred in the absence of any change in plasma dopamine. The octopamine metabolite para-hydroxyphenylglycol, which was initially elevated at least 10-fold, also increased after metyrosine treatment. The unexpected increase of DOPA (progressively more converted toward DOPA sulfate) in the presence of tyrosine hydroxylase inhibition and increase in tyrosine may result from channeling the excess tyrosine toward DOPA and melanin through tyrosinase. Increases in plasma dopamine sulfate and urinary dopamine suggest that dopamine sulfate may be generated via DOPA sulfate and urinary dopamine may originate from circulating DOPA. Tyrosine hydroxylase inhibition may thus result in DOPA generation in non-catecholamine-producing tissues by an alternative pathway. The resulting progressive increase in DOPA and its sulfate may lead to increased urinary dopamine. DOPA sulfate may be an alternative source of dopamine sulfate.

DrugBank Data that Cites this Article

Pharmaco-metabolomics

Drug	Drug Groups	Metabolite	Change	Description
Metyrosine	Approved	Dihydroxyphenylethanol	increased	Metyrosine increases the level of Dihydroxyphenylethanol in the blood
Metyrosine	Approved	Dopamine sulfate	increased	Metyrosine increases the level of Dopamine sulfate in the blood
Metyrosine	Approved	Tyrosine	increased	Metyrosine increases the level of Tyrosine in the blood
Metyrosine	Approved	DOPA	increased	Metyrosine increases the level of DOPA in the blood
Metyrosine	Approved	Sulfate ester of DOPA	increased	Metyrosine increases the level of Sulfate ester of DOPA in the blood
Metyrosine	Approved	Sulfate ester of dopamine	increased	Metyrosine increases the level of Sulfate ester of dopamine in the blood