Investigation of Trace Amine Metabolism in the Central Nervous System through Measurements on Cerebrospinal Fluid

Abstract

The metabolism of trace amines in the CNS can be studied through measurement of their product acids in the CSF. Animal studies suggest that an appreciable amount of tryptamine in the brain is derived from the periphery and diffuses into the brain. The same is probably true for phenylethylamine. Phenylethylamine is metabolized in human brain at about the same rate as the biogenic amines and p-tyramine at about half that rate. Tryptamine metabolism is only somewhat slower, while m-tyramine metabolism is a quantitatively minor pathway. Tryptophan availability is an important controlling factor for tryptamine turnover while aromatic amino acid decarboxylase levels are important for both tryptamine and phenylethylamine. Unlike biogenic amine metabolism, trace amine metabolism does not seem to be influenced in any important way by the age or sex of the subject. Human brain tryptamine metabolism is increased by melatonin administration, possibly due to its action on the activity of aromatic amino acid decarboxylase. In narcolepsy and idiopathic hypersomnia CSF levels of the tryptamine metabolite, indoleacetic acid, and of dopamine, are low. As both tryptamine and dopamine are present in brain at the highest levels in the basal ganglia, this brain region is implicated in the pathophysiology of hypersomnia. CSF indoleacetic acid was elevated in hepatic coma, the elevation being related to the grade of coma. This is consistent with the trace amine/false transmitter hypothesis of hepatic coma.