Studies on the metabolism of D- and L-isomers of 3,4-dihydroxyphenylalanine (DOPA). IV. Urinary and tissue metabolites of D- and L-DOPA-14C after intravenous and oral administration to rats.

Abstract

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.