Metabolism of 3-Hydroxytyramine (cas 51-61-6) (dopamine) in human subjects

Add time:07/11/2019    Source:sciencedirect.com

Six male subjects were infused with 104·6 μc 3-Hydroxytyramine (cas 51-61-6)-2-C14 (dopamine). The hydroxytyramine was dissolved in 1000 ml physiological saline and infused at a constant rate for 4 hr. Urine was collected at the end of the infusion period and at 2-hr intervals for the first 4 hr post infusion, and then at 8 hr, 24 hr and daily for the next 4 days. The urinary hydroxytyramine and its direct metabolites as well as its products, i.e. noradrenaline and its metabolites, were separated by column fractionation and identified. A new method, herein described, was used which simultaneously monitored the optical density and measured the radioactivity of each compound as it was eluted from the column. During the infusion, 38·9 per cent of the infused dose was recovered in urine as hydroxytyramine, noradrenaline, adrenaline (trace amounts) and their respective metabolites; recovery of hydroxytyramine accounted for 9·1 per cent while 3-methoxy-4-hydroxyphenylacetic acid accounted for 53·1 per cent of the radioactivity recovered during the infusion period; noradrenaline represented 4·7 per cent during the same period. The total amount of radioactivity recovered after 5 days was 97·2 ± 3·5 per cent. Approximately 75 per cent of the infused hydroxytyramine 2-C14 was directly metabolized into hydroxytyramine-related metabolic products. They are 3-methoxytyramine, 3-methoxy-4-hydroxyphenylacetic acid; 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethanol, 3-methoxy-4-hydroxyphenylethanol and their respective conjugates, as well as the conjugates of hydroxytyramine and several unknowns. Of these, 3-methoxy-4-hydroxyphenylacetic acid is by far the largest, since it represents 18·6 per cent of the infused dose recovered during the infusion period. The remaining 25 per cent of the infused hydroxytyramine was synthesized into noradrenaline and appeared in the urine as noradrenaline or metabolic products of noradrenaline, principally the latter. These experiments avoid many of the pitfalls and errors imposed by infusing exogenous labeled noradrenaline where one measures the metabolic products of circulating exogenous noradrenaline rather than the natural occurring noradrenaline. Furthermore, they provide more accurate and detailed information with regard to the rate of appearance and excretion of endogenous noradrenaline metabolites in the human.

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