Cerebrospinal fluid probenecid studies: a reinterpretation

Probenecid is used to block the transport of acid monoamine metabolites from cerebrospinal fluid (CSF), on the assumption that the resultant rise in CSF concentrations of the metabolites will reflect presynaptic "turnover" of the parent monoamine. However, CSF levels of probenecid correlate with CSF levels of the metabolite, suggesting that the blockade is incomplete at the probenecid levels obtained in human studies. This article reviews the literature on CSF probenecid-metabolite correlations and presents data demonstrating variations in the correlations across diagnostic groups. These cross-diagnostic variations may be due to group differences in membrane transport characteristics and and confound attempts to "correct for" CSF probenecid concentrations in studies of monoamine turnover.