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The influence of probenecid on the metabolism of serotonin, dopamine and their precursors in man

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Abstract

Probenecid inhibits the efflux of acid monoamine (MA) metabolites from the CNS. The probenecid-induced accumulation of these metabolites in the CSF in man supplies data on the central turnover of the corresponding amines. In this study an attempt was made to establish whether probenecid also exerts an influence on the metabolism of the MA precursors: tryptophan and tyrosine. The principal conclusions were the following.

  1. 1.

    Whereas in rats probenecid lowers the serum tryptophan level and elevates that in the brain (probably as a result of interference with the binding of tryptophan to serum albumins), the serum tryptophan level in human individuals is also lowered but the CSF concentration remains unchanged. After an oral tryptophan load, however, the CSF tryptophan concentration does increase.It is suggested that in man, endogenously released and exogenous tryptophan enter different metabolic pools in the brain.

  2. 2.

    After an oral load of 1-tryptophan, for the most part depressive patients showed a more rapid increase in CSF tryptophan concentration and a less marked rise of the CSF 5-HIAA level than did the psychologically undisturbed test subjects examined by Eccleston et al. It seems possible that, in the depressive patient, the tryptophan-metabolizing capacity is disturbed.

  3. 3.

    After an oral load of 1-tryptophan the CSF HVA concentration increased. Possibly, tryptophan is transformed to 5-HT in dopaminergic neurons, and this 5-HT may supersede the DA from the storage sites. This effect may well be of significance in the therapeutic application of 5-HT precursors.

  4. 4.

    The CSF concentrations of 5-HIAA, HVA, tryptophan and tyrosine show no systematic variations during the day.

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Authors and Affiliations

  1. Departments of Biological Psychiatry and Clinical Psychology, Psychiatric University Clinic, Groningen, The Netherlands

    H. M. van Praag, F. Flentge, J. Korf, L. C. W. Dols & T. Schut

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  1. H. M. van Praag
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  2. F. Flentge
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  3. J. Korf
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  4. L. C. W. Dols
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  5. T. Schut
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van Praag, H.M., Flentge, F., Korf, J. et al. The influence of probenecid on the metabolism of serotonin, dopamine and their precursors in man. Psychopharmacologia 33, 141–151 (1973). https://doi.org/10.1007/BF00429084

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  • DOI: https://doi.org/10.1007/BF00429084

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