Brain dopamine turnover and the relief of parkinsonism.

Levodopa alone or combined with a decarboxylase inhibitor elevated the concentration of homovanillic acid (HVA) in the cerebrospinal fluid (CSF). This increase correlated significantly with the dose of the drug but not with the clinical improvement, although some correlations with clinical side effects were evident. Nevertheless, the concentrations of HVA in the CSF during combined treatment were considerably lower than with therapeutically equivalent doses of levodopa alone. Obviously, a part of the HVA found in the CSF during levodopa treatment originates from the capillary walls. Treatment with dopamine receptor agonists, Piribedil or Bromocriptine decreased significantly both the basal level and probenecid- induced accumulations of HVA and CSF. But there were no changes in concentrations of 5-hydroxyindoleacetic acid (5-HIAA). Correlation analyses showed that patients who improved with both dopamine agonists used had significantly lower probenecid response of HVA in the CSF and less severe disease than those without beneficial effect. This relationship between dopamine receptor activation and improvement of parkinsonian disability suggests that the therapeutic efficacy of dopamine receptor agonists depends on the functional capacity of brain dopaminergic mechanisms.