5-Hydroxytryptophan

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5-Hydroxytryptophan
IUPAC name	2-amino-3- (5-hydroxy-1H-indol-3-yl) propanoic acid
Identifiers
CAS number	[56-69-9]
PubChem	144
MeSH	5-Hydroxytryptophan
SMILES	C1=CC2=C(C=C1O)C (=CN2)CC(C(=O)O)N
ChemSpider ID	388413
Properties
Molecular formula	C11H12N2O3
Molar mass	220.23 g/mol
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox references

5-Hydroxytryptophan or 5-HTP is a naturally occurring amino acid, a precursor to the neurotransmitter serotonin and an intermediate in tryptophan metabolism. It is marketed in the United States and other countries as a dietary supplement for use as an antidepressant, appetite suppressant, and sleep aid. However, according to a 2001 meta-analysis, insufficient high quality research has been done to establish that it is effective.^[1] Because it is naturally occurring it has not been sought to be approved as a drug in any country.

[edit] 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.^[2]

This reaction occurs both in nervous tissue and in the liver.^[3] 5-HTP crosses the blood-brain barrier, while 5-HT does not. Excess 5-HTP, especially when administered with Vitamin B6, is thought to be metabolized and excreted.^[4][5]

[edit] Pharmacology

The psychoactive action of 5-HTP is thought to derive from its effect on serotonin synthesis in central nervous system tissue. It is believed that an artificially high supply of 5-HTP causes the brain's serotonin-producing neurons to increase production. Increased serotonin production then leads to increased serotonin release and generally improved mood.

Research shows that co-administration with carbidopa greatly increases plasma 5-HTP levels.^[6] However, several studies have reported that 5-HTP is effective even without a peripheral decarboxylase inhibitor (e.g. carbidopa).^[7][8] Other studies have indicated the risk of a scleroderma-like condition resulting from the combination of 5-HTP and carbidopa.^[9]

[edit] As a therapeutic supplement

5-HTP, which is found in minute amounts in certain foods like cheese and the white meat of poultry,^{[citation needed]} is often sold as an over-the-counter therapeutic supplement. In this case, it is usually sourced from the seeds of Griffonia simplicifolia. 5-HTP in supplement form is typically sold in 50 mg or 100 mg gelatin or vegetarian capsules.

[edit] Research

5-HTP has been studied and shown to be of benefit in the following conditions: Primary fibromyalgia syndrome, Friedreich's ataxia, LSD-induced psychosis, chronic headaches (primary or otherwise), depression, binge eating associated with obesity, and insomnia.

J Int Med Res. 1990 May-Jun;18(3):201-9. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. Arch Neurol. 1995 May;52(5):456-60. Levorotatory form of 5-hydroxytryptophan in Friedreich's ataxia. Results of a double-blind drug-placebo cooperative study. Am J Psychiatry. 1983 Apr;140(4):456-8. L-5-hydroxytryptophan for LSD-induced psychosis. J Neurosurg Sci. 1985 Jul-Sep;29(3):239-48. Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. Altern Med Rev. 1998 Aug;3(4):271-80.5-Hydroxytryptophan: a clinically-effective serotonin precursor.

A recent (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."^[10]

Metabolic pathway from tryptophan to serotonin.

[edit] 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 has been sold since the 1990's in the US otc without any serious problems reported.

Due to the conversion of 5-HTP into serotonin by the liver, there is a possible yet unproven risk of heart valve disease from serotonin's effect on the heart.^{[11][12][original research?]}

Direct and indirect evidence for possible yet unproven risks and side effects associated with 5-HTP when overdosed:

In people:

• Heart valve damage or disease.^{[11][12][original research?]}
• When combined with MAO inhibitors, MDMA, Methylone, SSRIs, or other serotoninergic drugs 5-HTP may cause acute serotonin syndrome.^{[citation needed]}
• When combined with carbidopa (as a treatment for symptoms of Parkinson's disease), 5-HTP causes nausea and vomiting; however this can be alleviated via administration of granisetron.^[13]

[edit] See also

• Serotonin
• Tryptophan
• Vitamin B6
• Pyridoxal Phosphate (PLP) - Bioactive form of vitamin B6

[edit] References

[edit] Further reading

• den Boer JA, Westenberg HG (1990). "Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder". Psychiatry research 31 (3): 267–78. doi:10.1016/0165-1781(90)90096-N. PMID 2139731. 

• Angst J, Woggon B, Schoepf J (1977). "The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study". Archiv für Psychiatrie und Nervenkrankheiten 224 (2): 175–86. PMID 336002. 
• article at Psychology Today

• Turner EH, Loftis JM, Blackwell AD (2006). "Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan". Pharmacol. Ther. 109 (3): 325–38. doi:10.1016/j.pharmthera.2005.06.004. PMID 16023217. 
• 5-Hydroxytryptophan (5-HTP) Supplement Information at University of Maryland Medical Center