Metabolism of L-DOPS in Animals

The metabolism of (−)-(2S, 3R)-2-amino-3-hydroxy-3-(3, 4-dihydroxyphenyl) propionic acid (L-DOPS), an unphysiological amino acid and the precursor of (−)-norepinephrin (NE) was investigated in mice, rats, dogs and Rhesus monkeys after oral administration of 14C-L-DOPS labelled at C-3 position. 1. L-DOPS, (−)-(2S, 3R)-2-amino-3-hydroxy-3-(4-hydroxy-3-methoxyphenyl) propionic acid (3-OM-DOPS), 3, 4-dihydroxybenzoic acid (PA), 4-hydroxy-3-methoxybenzoic acid (VA) and their conjugates were identified as the major metabolites in urine of mice, rats, dogs and Rhesus monkeys after oral administration of 14C-L-DOPS (10 and 100 mg/kg). In addition, 3, 4-dihydroxytoluene (HC) was identified in urine of rats and Rhesus monkeys. 2. The concentration of unchanged L-DOPS in serum, liver and urine was larger than those of other metabolites. After oral administration of 14C-L-DOPS (10 mg/kg), amounts of L-DOPS, 3-OM-DOPS, PA (Conjugate) and VA (Conjugate) excreted in urine were 10 ?? 20 %, 6 ?? 15 %, 10 ?? 20 % and 2 ?? 11 % of the dose, respectively. In urine of rats and Rhesus monkeys, a trace amount of the conjugate of HC was detected. 3. Amounts of NE and its metabolite in serum and urine of amimals, after oral administrtion of 14C-L-DOPS increased evidently, in comparison with their baseline values observed before L-DOPS administration. In every animal administered with 14C-L-DOPS, the total excretion of NE and its metabolite to urine was less than 1 % of the dose. 4. The concentration of NE in kidney of rats, after sigle oral administration of 14C-L-DOPS (10 mg/kg), was about 6 times higher than that in kidney of Rhesus monkeys.