Homovanillic and 5-Hydroxyindeleacetic Acids in Cerebrospinal Fluid After Probenecid: Measurement of Brain Monoamine Oxidase Inhibition in Vivo

Summary

The effects of inhibition of monoamine oxidase (MAO) by pargyline on the concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) of dogs are reported. Administration of pargyline reduced control levels of HVA and 5-HIAA and inhibited the probenecid-induced rise of these acid metabolites. The magnitude of this inhibition was related to the dose of pargyline. Pargyline inhibited the probenecid-induced rise in HVA more effectively than the rise in 5-HIAA, suggesting the existence of different monamine oxidases in dog brain. After completion of the pargyline treatment, the probenecid-induced rise of 5-HIAA and HVA returned to normal in about 1 month. Measurement of the acid metabolites in the CSF is a direct index not only of the MAO activity in brain but of the degree to which the metabolism of a specific monoamine is inhibited. Probenecid treatment makes this method sensitive enough that it might be applied for measurement of brain MAO activity in clinical practice.