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. 1980 Dec;10(6):611–615. doi: 10.1111/j.1365-2125.1980.tb00517.x

Metabolism of an oral tryptophan load. II: Effect of pretreatment with the putative tryptophan pyrrolase inhibitors nicotinamide or allopurinol.

A R Green, J K Aronson, G Curzon, H F Woods
PMCID: PMC1430225  PMID: 6451235

Abstract

1 The effect of seven days administration of either allopurinol (300 mg daily) or nicotinamide (500 mg twice daily) on the metabolism of an oral L-tryptophan load (50 mg/kg) has been investigated. 2 Administration of either drug failed to alter the plasma total or free tryptophan or plasma kynurenine curve. Nor was the urinary excretion of tryptophan, kynurenine, 5-hydroxyindoleacetic acid or indole acetic acid influenced. 3 Allopurinol pretreatment did increase the volume of distribution of tryptophan. 4 These data suggest that allopurinol and nicotinamide are unlikely to be of value as tryptophan pyrrolase inhibitors in vivo and therefore would not increase the therapeutic effect of L-tryptophan when it is given to treat depressive illness.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Badawy A. A., Evans M. Letter: Tryptophan plus a pyrrolase inhibitor for depression. Lancet. 1975 Nov 1;2(7940):869–869. doi: 10.1016/s0140-6736(75)90258-5. [DOI] [PubMed] [Google Scholar]
  2. Badawy A. A., Evans M. Letter: Tryptophan plus a pyrrolase inhibitor for depression? Lancet. 1974 Nov 16;2(7890):1209–1210. doi: 10.1016/s0140-6736(74)90849-6. [DOI] [PubMed] [Google Scholar]
  3. Becking G. C., Johnson W. J. The inhibition of tryptophan pyrrolase by allopurinol, an inhibitor of xanthine oxidase. Can J Biochem. 1967 Nov;45(11):1667–1672. doi: 10.1139/o67-197. [DOI] [PubMed] [Google Scholar]
  4. Fernando J. C., Joseph M. H., Curzon G. Letter: Tryptophan plus a pyrrolase inhibitor for depression? Lancet. 1975 Jan 18;1(7899):171–171. doi: 10.1016/s0140-6736(75)91478-6. [DOI] [PubMed] [Google Scholar]
  5. Green A. R., Aronson J. K., Curzon G., Woods H. F. Metabolism of an oral tryptophan load. I: Effects of dose and pretreatment with tryptophan. Br J Clin Pharmacol. 1980 Dec;10(6):603–610. doi: 10.1111/j.1365-2125.1980.tb00516.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Green A. R., Curzon G. Decrease of 5-hydroxytryptamine in the brain provoked by hydrocortisone and its prevention by allopurinol. Nature. 1968 Dec 14;220(5172):1095–1097. doi: 10.1038/2201095a0. [DOI] [PubMed] [Google Scholar]
  7. Green A. R., Woods H. F., Joseph M. H. Tryptophan metabolism in the isolated perfused liver of the rat: effects of tryptophan concentration, hydrocortisone and allopurinol on tryptophan pyrrolase activity and kynurenine formation. Br J Pharmacol. 1976 May;57(1):103–114. doi: 10.1111/j.1476-5381.1976.tb07660.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Joseph M. H., Young S. N., Curzon G. The metabolism of a tryptophan load in rat brain and liver. The influence of hydrocortisone and allopurinol. Biochem Pharmacol. 1976 Dec 1;25(23):2599–2604. doi: 10.1016/0006-2952(76)90515-3. [DOI] [PubMed] [Google Scholar]
  9. Kageyama N. A direct colorimetric determination of uric acid in serum and urine with uricase-catalase system. Clin Chim Acta. 1971 Feb;31(2):421–426. doi: 10.1016/0009-8981(71)90413-x. [DOI] [PubMed] [Google Scholar]
  10. MCCOLLISTER R. J., GILBERT W. R., Jr, ASHTON D. M., WYNGAARDEN J. B. PSEUDOFEEDBACK INHIBITION OF PURINE SYNTHESIS BY 6-MERCAPTOPURINE RIBONUCLEOTIDE AND OTHER PURINE ANALOGUES. J Biol Chem. 1964 May;239:1560–1563. [PubMed] [Google Scholar]
  11. Møller S. E., Kirk L. The effect of allopurinol on the kynurenine formation in humans following a tryptophan load. Acta Vitaminol Enzymol. 1978;32(5-6):159–162. [PubMed] [Google Scholar]
  12. Shopsin B. Enhancement of the antidepressant response to L-tryptophan by a liver pyrrolase inhibitor: a rational treatment approach. Neuropsychobiology. 1978;4(3):188–192. doi: 10.1159/000117632. [DOI] [PubMed] [Google Scholar]
  13. Young S. N., Sourkes T. L. Antidepressant action of tryptophan. Lancet. 1974 Oct 12;2(7885):897–898. doi: 10.1016/s0140-6736(74)91233-1. [DOI] [PubMed] [Google Scholar]

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