Abstract

Radioactivity appeared rapidly in plasma following oral administration of N-alanyldopamine-¹⁴C (16.7 mg/kg) and dopamine-¹⁴C (15 mg/kg) to rats, dogs, rabbits, monkeys, guinea pigs, and mice. Most of the radioactive dose appeared in the urine of all species by 24 hr. Both N-alanyldopamine and dopamine were found to have the same general pathway of metabolism. However, there were considerable quantitative differences among dogs, rats, rabbits, mice, guinea pigs, and monkeys in their metabolism of these drugs. The main excretion product of both compounds in dog urine was dopamine sulfate ester; dogs carried out O-methylation in addition to deamination, which resulted in a relatively high content of homovanillic acid in dog urine. Almost every metabolite appeared in the conjugated form in mouse urine. In addition, mouse urine contained more than one-third of the total radioactivity as conjugated dopamine, mainly as the glucuronide but also as sulfate. Rats conjugated about one-third of the orally administered drug as dopamine glucuronide. All urinary metabolites of the drug were eliminated in the free form by the guinea pig. The guinea pig and rabbit excreted these metabolites mainly as oxidation products of the side chain. Since O-methylation was not extensive, the main metabolite in the rabbit and guinea pig was 3,4-dihydroxyphenylacetic acid. In monkey, both free and conjugated urinary metabolites were excreted; also dopamine sulfate content was quite high.