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Increase in the plasma concentration of free tryptophan caused by probenecid in humans

Abstract

Probenecid was administered orally in a dose of 1 g twice daily for 3 days to eight patients nutriated through a gastric tube with a standarized diet containing a known amount of tryptophan. Probenecid caused an increase by 52% (P<0.01) in the free (non protein-bound) concentration of tryptophan in plasma (from 1.22±0.16 to 1.86±0,28 Μg/ml; mean±SEM). The total (free + protein-bound) plasma tryptophan concentration was not significantly changed by the present dose of probenecid. There was a positive correlation (Spearmans rank correlation coefficient =0.74; P<0.05) between the increase in percentage free tryptophan and the achieved plasma concentration of probenecid. The cerebrospinal fluid (CSF) concentration of tryptophan was not significantly changed by probenecid (2 g/day during 21/2 days) given to another group of five patients.

It is concluded from the present study, that the increase in the CSF concentration of 5-hydroxyindoleacetic acid (5-HIAA) caused by probenecid, in addition to blockade of the 5-HIAA transport out of the CSF, might be explained by an increased rate of synthesis of brain serotonin since the availability of its precursor is increased due to the probenecid-induced increase in the plasma concentration of free tryptophan.

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Lewander, T., Sjöström, R. Increase in the plasma concentration of free tryptophan caused by probenecid in humans. Psychopharmacologia 33, 81–86 (1973). https://doi.org/10.1007/BF00428795

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Key words

  • 5-Hydroxyindole-Acetic Acid
  • Cerebrospinal Fluid
  • Probenecid
  • Tryptophan
  • Human Plasma