Effect of probenecid on endogenous and exogenous 3,4-dihydroxy-phenylacetic acid and homovanillic acid in the rat brain

Abstract

The two dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured in corpus striatum and hippocampus in rats after an intracerebroventricular injection of DOPAC or HVA. Probenecid 200 mg/kg i.p. increased the concentration of HVa by the same factor in both control animals and animals treated with HVA. Probenecid had no effect on the DOPAC concentration in control animals or in animals treated with DOPAC. After DOPAC intraventricularly some increase in the HVA concentration could be seen. Pargyline 75 mg/kg was given i.m. and the decline of HVA and DOPAC in corpus striatum was compared in animals with or without probenecid treatment (200 mg/kg i.p.). In the control animals DOPAC declined more rapidly than did HVA. In the probenecid-treated animals there was no change in the DOPAC curve while the HVA showed a slower elimination but still with an exponential curve. The conclusion is drawn that there is an active mechanism for the excretion of DOPAC which is not identical with the excretion mechanism fo HVA. A considerable part of the dopamine is directly deaminated to DOPAC in vivo and some of this DOPAC is probably O-methylated to HVA.