The radioactive metabolites of D-and L-isomers of 3,4-dihydroxyphenylalanine-(DOPA)-2-14C in the urine and the main tissues were comparatively investigated after intravenous and oral administration to rats. After administration of L-DOPA, eighteen metabolites were detected in the urine and dopamine conjugate, dopamine, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3 -methoxy-4 -hydroxyphenyl ethanol (MHPE) conjugate were found to be the main metabolites, while excretion as DOPA was only less than 1%. After administration of D-DOPA, an appreciable amount (20%) was excreted as unchanged DOPA, but dopamine, mostly in the free form, was found to be the main metabolite.After administration of L-DOPA, dopamine and its metabolites were the main component in the tissues including the brain and skeletal muscle, while after that of D-DOPA, 3-O-methyl-DOPA was the only metabolite, except the kidney where dopamine and its metabolites were found to be formed. It was demonstrated that approximately 67 and 53% of the brain radioactivity was dopamine and its metabolites at 10 and 60 min after intravenous and oral administration of L-DOPA-14C, respectively. The main metabolite in the pancreas and intestine from L-DOPA was DOPAC and dopamine conjugate, respectively, while unchanged DOPA from D-DOPA. In the liver, where D-DOPA dose not accumulate, dopamine conjugate was the main metabolite from L-DOPA, while no dopamine from D-DOPA. From these results, D-DOPA was considered to be metabolized to dopamine only in the kidney, most of which is excreted directly into the urine.In the previous papers,1,4,5) the absorption, distribution and excretion of radioactivity were compared between 14C-labeled D-and L-isomers of 3,4-dihydroxyphenylalanine (DOPA) following intravenous and oral administration to rats. The results revealed that there are marked differences in the fates of the two isomers, which could be interpreted as being due to specificity in the transport and metabolic systems with respect to the optical isomers. The present investigations were performed to establish further the relation between the distribution of radioactivity and the metabolic fates of the two isomers. The radioactive metabolites of D-and L-DOPA-14C in the urine and the main tissues including the brain were comparatively investigated following the intravenous and oral administration to rats.
