Clinical application of the probenecid test for measurement of monoamine turnover in the CNS.

The probenecid-induced accumulation of the acidic metabolites of dopamine and serotonin is widely used to estimate the CNS turnover of these amines in human subjects. The theoretical basis of the probenecid test is discussed, including the assumptions on which the test is based, and the limitations of the procedure. Suggestions are offered on appropriate methods for analyzing test data. Available evidence suggests that maximal inhibition of the efflux of the acidic metabolites of dopamine and serotonin from the CSF is not achieved with probenecid doses up to 100 mg/kg. Therefore, before a comparison can be made between the accumulation of CSF metabolites from different groups of subjects, a correction for CSF probenecid concentrations is necessary. Moreover, in addition to the measurement of dopamine and serotonin turnover, the probenecid test can be extended to include comparisons of CNS turnover of other monoamines including octopamine, p-tyramine, and tryptamine.