Central Monoamine Metabolism in Parkinson's Disease

Abstract

Basal concentrations and probenecid-induced accumulations of homovanillic acid (HVA), a major metabolite of dopamine, in the lumbar cerebrospinal fluid (CSF) of parkinsonian patients were markedly below those of control subjects. Although steady state levels of 5-hydroxyindoleacetic acid (5-HIAA) did not differ significantly from control values, there was a substantial diminution in the response of this serotonin metabolite to probenecid. Since probenecid inhibits the clearance of HVA and 5-HIAA from CSF, these results suggest that a concomitant reduction in the central metabolism of serotonin and dopamine attends clinically advanced Parkinson's disease. Pretreatment severity of parkinsonian rigidity and bradykinesia, but not tremor, correlated inversely with the probenecid-induced rise in both monoamine metabolites. There was, however, no apparent association between the therapeutic response to levodopa and either the severity of parkinsonian signs prior to therapy or the magnitude of the defect in monoamine metabolism.