Disposition of homovanillic acid in the primate

Prior studies have shown that homovanillic acid is the principal metabolite of dopamine in the primate central nervous system (CNS). In studies of primates given deuterated homovanillic acid systemically, however, only 50% of the administered amounts have been recovered in the urine over the next 4-48 hr. These findings have left it unclear whether there is a slowly turning-over compartment of homovanillic acid, conversion of homovanillic acid to another compound, or excretion of homovanillic acid from the body by a nonrenal route. We synthesized [3H]homovanillic acid and administered it intravenously to four rhesus monkeys. Over the subsequent 4 hr, 94.9 +/- 8.9% (SD) of the administered radioactivity was recovered in the urine, almost entirely as homovanillic acid. These results are consistent with the interpretation that, in primates, there is not a major body pool of homovanillic acid with slow turnover, nor is metabolism to other compounds significant, nor is there evidence for nonrenal excretion.