Abstract

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.