European Journal of Clinical Pharmacology

, Volume 23, Issue 1, pp 81–86

Human pharmacokinetics of long term 5-hydroxytryptophan combined with decarboxylase inhibitors

  • I. Magnussen
  • M. H. Van Woert
Originals

Summary

L-5-Hydroxytryptophan (5HTP) and its major metabolites 5-hydroxytryptamine (5HT) and 5-hydroxyindoleaceticacid (5HIAA) were measured in blood and cerebrospinal fluid from neurological patients receiving steady state treatment with 5HTP. There was accumulation of 5HT in blood platelets and 5HIAA in plasma in all patients, despite concomitant administration of the L-aromatic amino acid decarboxylase inhibitors, carbidopa and benserazide. There was no correlation between the 5HTP dose and the circulating concentrations of the amino acid or its metabolites. Preliminary comparison of the biochemical and therapeutic effects of carbidopa versus benserazide suggest that 5HTP: carbidopa is superior to 5HTP: benserazide. A direct proportionality between plasma 5HTP concentrations and the levels of 5HTP in the lumbar cerebrospinal fluid was found. The binding to serum proteins of 5HTP in the clinically relevant concentration range of 10 to 100 µM was investigated; 19% of circulating 5HTP was bound to serum proteins. 5HTP did not displace protein-bound tryptophan in serum.

Key words

benserazide carbidopa serotonin 5HTP-treatment metabolism decarboxylase inhibitors cerebrospinal fluid metabolites protein binding 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Van Woert MH, Rosenbaum D (1979) L-5-Hydroxytryptophan terapy in myoclonus. Adv Neurol 26: 107–122Google Scholar
  2. 2.
    Magnussen I, Engbaek F (1978) The effects of aromatic amino acid decarboxylase inhibitors on plasma concentrations of 5-hydroxytryptophan in man. Acta Pharmacol Toxicol 43: 36–42Google Scholar
  3. 3.
    Magnussen I, Jensen TS, Rand JH, Van Woert MH (1981) Plasma accumulation and metabolism of orally single dose administered L-5-hydroxytryptophan in man. Acta Pharmacol Toxicol 49: 184–189Google Scholar
  4. 4.
    Magnussen I, Nielsen-Kudsk F (1980) Bioavailability and related pharmacokinetics in man of orally administered 5-hydroxytryptophan in steady state. Acta Pharmacol Toxicol 46: 257–262Google Scholar
  5. 5.
    Van Woert MH, Jutkowitz R, Rosenbaum D, Bowers MB (1976) Serotonin and myoclonus. Monogr Neural Sci 3: 71–80Google Scholar
  6. 6.
    Borga O, Azarnoff DL, Forshell GP, Sjöquist F (1969) Plasma protein binding of tricyclic antidepressants in man. Biomed Pharmacol 18: 2135–2143Google Scholar
  7. 7.
    Engbaek F, Magnussen I (1978) Determination of 5-hydroxytryptophan in plasma by high-performance liquid chromatography and fluorometric detection after phthaldialdehyde reaction. Clin Chem 24: 376–378Google Scholar
  8. 8.
    Shindo H, Komai T, Kawei K (1977) Mechanism of intestinal absorption and brain uptake of L-5-hydroxytryptophan in rats, as compared to those of L-3, 4-dihydoxyphenyl-alanine. Chem Pharm Bull 25: 1417–1425Google Scholar
  9. 9.
    Bianchine JR, Preziosi TJ, Hsu TH, Messine FS (1971) L-Alpha-methyldopa hydrazine (MK-486) and L-Dopa: A double-blind trial in parkinsonism. Pharmacologist 13: 231Google Scholar
  10. 10.
    Barbeau A (1973) Treatment of Parkinson's disease with L-DOPA and R04-4602. Review and present states. In: Jahr MD (ed) Adv. in Neurology, Vol. 2, Raven Press, New York, pp 173–198Google Scholar
  11. 11.
    Rosengren E (1960) Are dihydroxyphenylalanine decarboxylase and 5-hydroxytryptophan decarboxylase individual enzymes? Acta Physiol Scand 49: 364–369Google Scholar
  12. 12.
    Lovenberg W, Weissbach H, Udenfriend S (1962) Aromatic L-amino acid decarboxylase. J Biol Chem 237: 89–93Google Scholar
  13. 13.
    Born GAV, Gillson RE (1959) Studies in the uptake of 5-hydroxytryptamine by blood platelets. J Physiol (Lond) 146: 472–491Google Scholar
  14. 14.
    Costa JL, Stark H, Shafer B, Corash L, Smith MA, Murphy DL (1978) Maximal packet size for serotonin in storage vesicles of intact human platelets. Life Sci 23: 2193–2198Google Scholar
  15. 15.
    Marmaras VJ, Mimikos N (1971) Enzyme formation of serotonin in mammalian blood platelets and red cells. Experientia 27: 196–197Google Scholar
  16. 16.
    Paasonen MK (1973) Blood platelets as a model for aminergic neurons. In: Bloom FE, Acheson GH (ed) Pharmacology and the future of man, Vol. 4. S Karger, Basel, pp 328–342Google Scholar
  17. 17.
    Clark CT, Weissbach H, Udenfriend S (1954) 5-hydroxytryptophan decarboxylase: Preparation and properties. J Biol Chem 210: 139–148Google Scholar
  18. 18.
    Burkhard WP, Gey KF, Pletcher A (1964) Inhibition of decarboxylase of aromatic amino acids by 2, 3, 4-trihyoxybenzylhydrazine and its seryl derivative. J Biochem Biophs 107: 187–196Google Scholar
  19. 19.
    Porter CC (1973) Inhibitors of aromatic amino acid decarboxylase their biochemestry. Adv Neurol 2: 37–45Google Scholar
  20. 20.
    Wirz-Justice A, Puhringer W, Lacoste V, Graw P, Gastpar M (1976) Intravenous L-5-hydroxytryptophan in normal subjects: An interdisciplinary precursor loading study. Part III: Neuroendocrinological and biochemical changes. Pharmakopsychiatry 9: 277–288Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • I. Magnussen
    • 1
    • 2
  • M. H. Van Woert
    • 1
    • 2
  1. 1.Department of NeurologyMount Sinai School of MedicineNew YorkUSA
  2. 2.the Department of Neurology and the Research Laboratory for Metabolic Disorders, Department of Clinical ChemistryUniversity of AarhusAarhusDenmark

Personalised recommendations