Oct 2, 2012

5-Hydroxytryptophan - Wikipedia, the free encyclopedia

5-Hydroxytryptophan - Wikipedia, the free encyclopedia

5-Hydroxytryptophan

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Not to be confused with serotonin (5-hydroxytryptamine, 5-HT).
 This article may be too technical for most readers to understand. Please help improve this article to make it understandable to non-experts, without removing the technical details. The talk page may contain suggestions. (February 2012)
5-Hydroxytryptophan
Identifiers
CAS number 56-69-9 Yes
PubChem 144
ChemSpider 388413 Yes
UNII C1LJO185Q9 Yes
KEGG D07339 Yes
MeSH 5-Hydroxytryptophan
ChEBI CHEBI:17780 Yes
ChEMBL CHEMBL350221 Yes
Jmol-3D images Image 1
Properties
Molecular formula C11H12N2O3
Molar mass 220.23 g/mol
 Yes (verify) (what is: Yes/?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references
5-Hydroxytryptophan (5-HTP), also known as oxitriptan (INN), is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitters serotonin and melatonin from tryptophan.
5-HTP is sold over-the-counter in the United Kingdom, United States and Canada as a dietary supplement for use as an antidepressant, appetite suppressant, and sleep aid, and is also marketed in many European countries for the indication of major depression under trade names like Cincofarm, Levothym, Levotonine, Oxyfan, Telesol, Tript-OH, and Triptum.[1][2] Several double-blind placebo-controlled clinical trials have demonstrated the effectiveness of 5-HTP in the treatment of depression,[1] though a lack of high quality studies has been noted.[3] More and larger studies are needed to determine if 5-HTP is truly effective in treating depression.[4]

Contents

Metabolism

5-Hydroxytryptophan is decarboxylated to serotonin (5-hydroxytryptamine or 5-HT) by the enzyme aromatic-L-amino-acid decarboxylase with the help of vitamin B6.[5] This reaction occurs both in nervous tissue and in the liver.[6] 5-HTP crosses the blood–brain barrier,[7] while 5-HT does not. Excess 5-HTP, especially when administered with Vitamin B6, is thought to be metabolized and excreted.[8][9]
5-HTP AAAD Serotonin
5-Hydroxy-L-Tryptophan (5-HTP).svg   Serotonin (5-HT).svg
PLP
Biochem reaction arrow foward YNNN horiz med.png


 
 

Pharmacology

The psychoactive action of 5-HTP is derived from its effect on the production of serotonin in central nervous system tissue. More specifically, 5-HTP increases the production of serotonin.[10]
Metabolic pathway from tryptophan to serotonin.
Research shows that co-administration with carbidopa greatly increases plasma 5-HTP levels.[11] However, several studies have reported that 5-HTP is effective even without a peripheral decarboxylase inhibitor (e.g. carbidopa).[12] Other studies have indicated the risk of a scleroderma-like condition resulting from the combination of 5-HTP and carbidopa.[13]

Dietary sources

Though 5-HTP is found in food only in insignificant quantities, it is a chemical involved intermediately in the metabolism of tryptophan, an amino acid found in turkey, milk, potatoes, pumpkin, and various greens.[14] See also the section Dietary sources of the article on L-tryptophan.

Therapeutic use

5-HTP is sold over-the-counter in the United States, the United Kingdom, and Canada as a dietary supplement for use as an antidepressant, appetite suppressant, and sleep aid. 5-HTP in supplement form is typically sold in 50 mg or 100 mg gelatin or vegetarian capsules. It is usually sourced from the seeds of Griffonia simplicifolia.
5-HTP has been studied and shown to be of benefit in the following conditions: primary fibromyalgia syndrome,[15] Friedreich's ataxia,[16] depression, anxiety, binge eating associated with obesity, and insomnia.[17] There is no statistically significant difference between 5-HTP and placebo in treating chronic headaches (primary or otherwise).[18]
A 2001 meta-analysis found that of 108 studies on 5-HTP published between 1966 and 2000, only two met the authors' quality standards for inclusion. The two studies that were deemed of sufficient quality did not deal with 5-HTP exclusively, instead combining results for 5-HTP and tryptophan, so the results may not be completely applicable for 5-HTP alone. While the combined analysis of the two 5-HTP and tryptophan studies showed significant effectiveness over placebo in treating depression, the authors state that overall "the evidence was of insufficient quality to be conclusive". They also state that "because alternative antidepressants exist which have been proven to be effective and safe, the clinical usefulness of 5-HTP and tryptophan is limited at present".[3]

Possible risks or side effects

Because 5-HTP has not been thoroughly studied in a clinical setting, possible side effects and interactions with other drugs are not well known. However, it is noteworthy that no published reports of serious side effects exist, despite that 5-HTP is freely available as a nutraceutical and has been administered to patients since the 50s, often chronically and often as co-therapy to other drugs, such as antidepressants.[19][20][21] This could indicate that serious side effects are relatively rare with 5-HTP, at least in moderate doses. On the other hand, acute moderate gastrointestinal effects, such as diarrhea and vomiting, are common upon administration of 5-HTP, probably due to rapid formation of serotonin in the upper intestinal tract.[19][22][23]
Injected serotonin has been shown to increase the risk of heart valve disease in animals.[24][25] 5-HTP has not been subjected to this test. Oral 5-HTP results in an increase in urinary 5-HIAA, a serotonin metabolite, indicating that 5-HTP is peripherally metabolized to serotonin, which is then metabolized. This might cause a false positive test in tests looking for carcinoid syndrome.[26]
5-HTP was found to increase plasma renin activity in rats, when not co-administered with a peripheral aromatic L-amino acid decarboxylase inhibitor, such as carbidopa or benserazide.[27]
Direct and indirect evidence for possible yet unproven risks and side effects associated with 5-HTP when overdosed:
It has been suggested that 5-HTP may cause eosinophilia-myalgia syndrome (EMS), a serious condition which results in extreme muscle tenderness, myalgia, and blood abnormalities. However, there is evidence to show that EMS was caused by a contaminant in early 5-HTP supplements, before the introduction of the current Good Manufacturing Practices by the United States FDA in 2007. Many countries now employ similar regulation.[32]

See also

References

  1. ^ a b Turner EH, Blackwell AD (2005). "5-Hydroxytryptophan plus SSRIs for interferon-induced depression: synergistic mechanisms for normalizing synaptic serotonin". Medical Hypotheses 65 (1): 138–44. doi:10.1016/j.mehy.2005.01.026. PMID 15893130.
  2. ^ Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. ISBN 3-88763-075-0.
  3. ^ a b Shaw K, Turner J, Del Mar C (2002). Shaw, Kelly A. ed. "Tryptophan and 5-hydroxytryptophan for depression". Cochrane Database of Systematic Reviews (Online) (1): CD003198. doi:10.1002/14651858.CD003198. PMID 11869656.
  4. ^ 5-Hydroxytryptophan (5-HTP) University of Maryland Medical Center. 2011. Accessed: 9 January 2012.
  5. ^ Rahman MK, Nagatsu T, Sakurai T, Hori S, Abe M, Matsuda M (1982). "Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats". Jpn. J. Pharmacol. 32 (5): 803–11. doi:10.1254/jjp.32.803. PMID 6983619.
  6. ^ Bouchard, S; Bousquet, C; Roberge, AG (1981). "Characteristics of dihydroxyphenylalanine/5-hydroxytryptophan decarboxylase activity in brain and liver of cat". Journal of Neurochemistry 37 (3): 781–7. doi:10.1111/j.1471-4159.1982.tb12555.x. PMID 6974228.
  7. ^ Gomes P, Soares-da-Silva P. (1999). "L-DOPA transport properties in an immortalised cell line of rat capillary cerebral endothelial cells, RBE 4". Brain Res. 829 (1–2): 143–150. doi:10.1016/S0006-8993(99)01387-6. PMID 18445233.
  8. ^ Bouchard S, Roberge AG (1979). "Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat". Can. J. Biochem. 57 (7): 1014–8. doi:10.1139/o79-126. PMID 39668.
  9. ^ Amamoto T, Sarai K (1976). "On the tryptophan-serotonin metabolism in manic-depressive disorders. Changes in plasma 5-HT and 5-HIAA levels and urinary 5-HIAA excretion following oral loading of L-5HTP in patients with depression". Hiroshima J. Med. Sci. 25 (2–3): 135–40. PMID 1088369.
  10. ^ "5-HTP: Uses, Side Effects, Interactions and Warnings - WebMD". Archived from the original on 16 November 2009. Retrieved 2009-10-05.
  11. ^ Magnussen I, Jensen TS, Rand JH, Van Woert MH (1981). "Plasma accumulation of metabolism of orally administered single dose L-5-hydroxytryptophan in man". Acta pharmacologica et toxicologica 49 (3): 184–9. doi:10.1111/j.1600-0773.1981.tb00890.x. PMID 6175178.
  12. ^ Birdsall TC (1998). "5-Hydroxytryptophan: a clinically-effective serotonin precursor". Alternative medicine review : a journal of clinical therapeutic 3 (4): 271–80. PMID 9727088.
  13. ^ Sternberg EM, Van Woert MH, Young SN, et al. (1980). "Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa". N. Engl. J. Med. 303 (14): 782–7. doi:10.1056/NEJM198010023031403. PMID 6997735.
  14. ^ "5-Hydroxytryptophan". University of Maryland Medical Center. Archived from the original on 6 January 2010. Retrieved 2010-01-21.
  15. ^ Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V (1990). "Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome". The Journal of International Medical Research 18 (3): 201–9. PMID 2193835.
  16. ^ Trouillas P, Serratrice G, Laplane D, et al. (May 1995). "Levorotatory form of 5-hydroxytryptophan in Friedreich's ataxia. Results of a double-blind drug-placebo cooperative study". Archives of Neurology 52 (5): 456–60. doi:10.1001/archneur.1995.00540290042016. PMID 7733839. Retrieved 2009-07-30.
  17. ^ Birdsall TC (August 1998). "5-Hydroxytryptophan: a clinically-effective serotonin precursor". Alternative Medicine Review : a Journal of Clinical Therapeutic 3 (4): 271–80. PMID 9727088. Retrieved 2009-07-30.
  18. ^ De Benedittis G, Massei R (1985). "Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo". Journal of Neurosurgical Sciences 29 (3): 239–48. PMID 3913752.
  19. ^ a b Turner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006 Mar;109(3):325-38. Epub 2005 Jul 14. Review. PubMed PMID 16023217.
  20. ^ Byerley WF, Judd LL, Reimherr FW, Grosser BI. 5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects. J Clin Psychopharmacol. 1987 Jun;7(3):127-37. Review. PubMed PMID 3298325.
  21. ^ van Hiele LJ. l-5-Hydroxytryptophan in depression: the first substitution therapy in psychiatry? The treatment of 99 out-patients with 'therapy-resistant' depressions. Neuropsychobiology. 1980;6(4):230-40. PubMed PMID 6967194.
  22. ^ Gijsman HJ, van Gerven JM, de Kam ML, Schoemaker RC, Pieters MS, Weemaes M, de Rijk R, van der Post J, Cohen AF. Placebo-controlled comparison of three dose-regimens of 5-hydroxytryptophan challenge test in healthy volunteers. J Clin Psychopharmacol. 2002 Apr;22(2):183-9. PubMed PMID 11910264.
  23. ^ 1: Lowe SL, Yeo KP, Teng L, Soon DK, Pan A, Wise SD, Peck RW. L-5-Hydroxytryptophan augments the neuroendocrine response to a SSRI. Psychoneuroendocrinology. 2006 May;31(4):473-84. Epub 2005 Dec 27. PubMed PMID 16378695.
  24. ^ a b Gustafsson BI, Tømmerås K, Nordrum I, Loennechen JP, Brunsvik A, Solligård E, Fossmark R, Bakke I, Syversen U, Waldum H (March 2005). "Long-term serotonin administration induces heart valve disease in rats". Circulation 111 (12): 1517–22. doi:10.1161/01.CIR.0000159356.42064.48. PMID 15781732.
  25. ^ a b Xu J, Jian B, Chu R, Lu Z, Li Q, Dunlop J, Rosenzweig-Lipson S, McGonigle P, Levy RJ, Liang B (December 2002). "Serotonin Mechanisms in Heart Valve Disease II : The 5-HT2 Receptor and Its Signaling Pathway in Aortic Valve Interstitial Cells". Am. J. Pathol. 161 (6): 2209–18. doi:10.1016/S0002-9440(10)64497-5. PMC 1850896. PMID 12466135.
  26. ^ Joy T, Walsh G, Tokmakejian S, Van Uum SH (January 2008). "Increase of urinary 5-hydroxyindoleacetic acid excretion but not serum chromogranin A following over-the-counter 5-hydroxytryptophan intake". Can. J. Gastroenterol. 22 (1): 49–53. PMC 2659120. PMID 18209781.
  27. ^ Barney CC, Threatte RM, Kikta DC, Fregly MJ. (June 1981). "Effects of serotonin and L-5-hydroxytryptophan on plasma renin activity in rats". Pharmacol Biochem Behav. 14 (6): 895–900. doi:10.1016/0091-3057(81)90380-4. PMID 7019933.
  28. ^ Ma Z, Zhang G, Jenney C, Krishnamoorthy S, Tao R. (July 2008). "Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats". Eur J Pharmacol. 588 (2–3): 198–206. doi:10.1016/j.ejphar.2008.04.004. PMID 18499101.
  29. ^ Izumi T, Iwamoto N, Kitaichi Y, Kato A, Inoue T, Koyama T. (2006). "Effects of co-administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5-HT-related behavior in rats". Eur J Pharmacol. 532 (3): 258–264. doi:10.1016/j.ejphar.2005.12.075. PMID 16488409.
  30. ^ Jacobs G, Kamerling I, de Kam M, et al. (Nov 2008). "Enhanced tolerability of the 5-hydroxytryptophane challenge test combined with granisetron". J Psychopharmacol. (Oxford) 24 (1): 65–72. doi:10.1177/0269881108094299. PMID 18719048.
  31. ^ http://www.truestarhealth.com/Notes/1339004.html
  32. ^ Michelson, D; Page, SW, Casey, R, Trucksess, MW, Love, LA, Milstien, S, Wilson, C, Massaquoi, SG, Crofford, LJ, Hallett, M (1994 Dec). "An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan". The Journal of rheumatology 21 (12): 2261–5. PMID 7699627.

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