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Dopa, 3‐0‐methyldopa, and metabolites in urine during oral l ‐3‐0‐methyldopa therapy
Author(s) -
Sharpless Nansie S.,
Tyee Gertrude M.,
Muenter Manfred D.,
Dinapoli Robert P.
Publication year - 1974
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1974165part1770
Subject(s) - methyldopa , chemistry , urine , endocrinology , excretion , homovanillic acid , oral administration , metabolite , pharmacology , medicine , biochemistry , blood pressure , serotonin , receptor
The metabolic fate of orally administered l ‐3‐0‐methyldopa, given alone or with levodopa, was studied during a therapeutic trial in 5 patients with Parkinson's disease. During administration of 3‐0‐methyldopa alone, dopa was excreted in urine almost exclusively as a confugate hydrolyzable by Glusulase (mixture of sulfatase and β‐glucuronidase). Small increases in dopamine excretion confirmed that there had been some demethylation of 32‐0‐methyldopa. The small increase in 3‐methoxytyramine (3‐MT) excretion was greater than that of dopamine (DA), suggesting some direct decarboxylation of 3‐0‐methyldopa. Excretion of norepinephrine (NE) and epinephrine (E) and of their O‐methyl derivatives (normetanephrine [NM] and metanephrine [M]) was marginally affected by 3‐0‐methyldopa. Only small amounts of homovanillic acid (HVA) appeared in urine (2.3% of the dose), indicating that both decarboxylation and demethylation were minor routes of 3‐0‐methyldopa metabolism. Most of the 3‐0‐methyldopa dose was excreted unchanged or as vani/lactic acid (VLA). The proportion of the dose excreted as VLA increased linearly with increase in 3‐0‐methyldopa dosage, suggesting induction of transaminase. A paradoxic increase in vanilmandelic acid (VMA) excretion was observed during 3‐0‐methyldopa administration. Relative to the dose, the amount of VMA in urine was 7 times as great during administration of 3‐0‐methyldopa as during administration of levodopa.