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1 Research Department, F. Hoffmann-La Roche & Co. Ltd., Basle, Switzerland
The action of the dopa decarboxylase inhibitor Ro 4-4602 (N1-(DL-seryl)-N2-(2,3,4-trihydroxybenzyl) hydrazine) (50 mg/kg i.p.) on the metabolism of i.p. or p.o. administered C14-L-3,4-dihydroxyphenylalanine (dopa) has been investigated in brain, blood plasma and heart of rats. Thereby, the C14-amino acids (dopa and 3-O-methyldopa), the C14-catecholamines (dopamine and norepinephrine), as well as the C14-phenylcarboxylic acids (homovanillic and 3,4-dihydroxyphenylacetic acid), were determined. In the plasma and heart, Ro 4-4602 antagonizes the rise of C14-catecholamines and C14-phenylcarboxylic acids, but increases that of C14-amino acids. In the brain, the inhibitor enhances the C14-catecholamines (mainly C14-dopamine) as well as the C14-amino acids (mainly C14-dopa). The rise of C14-phenylcarboxylic acids is increased by Ro 4-4602 in the experiments with 16 mg/kg of C14-dopa but antagonized in those with 150 mg/kg of C14-dopa i.p. It is concluded that Ro 4-4602 inhibits the decarboxylation of C14-dopa in extracerebral tissues rather selectively. This probably leads to an increased penetration of C14-dopa from the blood into the brain, where it is then metabolized to C14-catecholamines.
Submitted on September 2, 1967
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