The influence of clofibrate (CPIB) on free and total tryptophan concentrations in rat serum and on brain concentrations of tryptophan, 5-hydroxytryptamine (5HT), and 5-hydroxyindolacetic acid (5HIAA) has been established. A single dose of CPIB administered orally caused a pronounced fall of total tryptophan, and a significant increase of free tryptophan in serum. Under the same experimental condition increases of brain tryptophan and 5HIAA concentrations were observed, with no change in brain 5HT. Similar modifications were observed after repeated administrations of the drug. From these results it may be inferred that CPIB increases brain 5HT synthesis by displacement of protein bound tryptophan in serum and thus by increasing in brain the availability of the substrate to tryptophan-hydroxylase.
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