THE METABOLIC PATHWAYS OF l-3-O-METHYLDOPA

¹ Research Department, F. Hoffmann-La Roche & Co. Ltd., Basel, Switzerland

After i.p. injection of l-3-¹⁴C-[3-methoxy-4-hydroxyphenyl]alanine (l-3-¹⁴C-O-methyldopa) to rats, small amounts of labeled catecholamines are found in the brain. In the urine, homovanillic acid, 3-methoxy-4-hydroxyphenyllactic acid, 3, 4-dihydroxvphenylacetic acid and O-methyldopa appear as the main radioactive compounds. In addition, minor amounts of labeled 3-methoxytyramine, 3, 4-dihydroxyphenylalanine and dopamine are excreted. Dopacetamide, an inhibitor of catechol-O-methyltransferase, enhances the urinary content of ¹⁴C-3, 4-dihydroxyphenylacetic acid and ¹⁴C-dopamine but decreases that of ¹⁴C-3-methoxytyramine. The major metabolite of ¹⁴C-3-methoxy-4-hydroxyphenyllactic acid in the urine of rats is ¹⁴C-homovanillic acid, but in addition some labeled O-methyldopa and catecholamines appear. The decarboxylation of l-1-¹⁴C-O-methyldopa (carboxyl-labeled) in vivo proceeds at a much slower rate than that of l-1-¹⁴C-3, 4-dihydroxyphenylalanine as judged by measurements of the expired ¹⁴CO₂. In conclusion, l-O-methyldopa seems to be metabolized by transamination and demethylation. It is uncertain whether direct decarboxylation may also occur to some extent.