5-Hydroxytryptophan
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IUPAC name
2-amino-3-(5-hydroxy-1H-indol-3-yl)propanoic acid
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Identifiers | |
3D model (
JSmol ) |
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ChEBI | |
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ChemSpider | |
ECHA InfoCard
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100.022.193 |
IUPHAR/BPS |
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KEGG | |
MeSH | 5-Hydroxytryptophan |
PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
C11H12N2O3 | |
Molar mass | 220.228 g·mol−1 |
Density | 1.484 g/mL |
Melting point | 298 to 300 °C (568 to 572 °F; 571 to 573 K) |
Boiling point | 520.6 °C (969.1 °F; 793.8 K) |
Pharmacology | |
N06AX01 (WHO) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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5-Hydroxytryptophan (5-HTP), also known as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin.
Uses
5-HTP is sold
A 2002 review concluded that although the data evaluated suggests that 5-HTP is more effective than placebo in the treatment of depression, the evidence was insufficient to be conclusive due to a lack of clinical data meeting the rigorous standards of the day.[2] More and larger studies using current methodologies are needed to determine if 5-HTP is truly effective in treating depression.[3][4] In small, controlled trials 5-HTP has also been reported to augment the antidepressant efficacy of the antidepressant clomipramine.[5][6][7] A 2020 meta-analysis found oral 5-HTP supplementation had a large effect size on depression symptom severity. However, the included studies were considered relatively weak and the methods and treatment duration varied between the seven studies examined.[8]
5-HTP use after MDMA
Other usage
At high doses, or in combination with carbidopa, 5-HTP has been used to treat obesity (by promoting weight loss).[9][10]
In clinical trials of various design, 5-HTP has also been reported to treat fibromyalgia,[11] myoclonus,[12] migraine,[13] and cerebellar ataxia.[14] However, these clinical findings, as for all therapeutic findings with 5-HTP, are preliminary and need confirmation in larger trials.
Drawbacks
5-HTP's short half-life (<2h)) are intended to, via novel delivery mechanisms, permit pain relief for up to twelve hours with an active ingredient which only provides relief for 3–6 hours. However, the inherent variability amongst different people with respect to drug metabolism makes this task challenging.
Side effects
Potential side effects of 5-HTP include
Interactions
When combined with antidepressants of the
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.[25] As mentioned below under pharmacology, cases of scleroderma-like illness have been reported in patients using carbidopa and 5-HTP.[26]
Oral 5-HTP results in an increase in urinary
It has been suggested that 5-HTP may cause
Production
5-HTP is produced from the amino acid
Absorption
After oral administration, 5-HTP is absorbed by the upper intestine.[15] The mode of absorption is not known, but presumably involves active transport via amino acid transporters. 5-HTP is adequately absorbed via oral cavity.[34] With a decarboxylase inhibitor, the bioavailability of 5-HTP can be higher than 50%.[35]
Pharmacokinetics
5-HTP is rapidly absorbed with a tmax of ≈1.5 h, and rapidly eliminated with a half-life of ≈1.5 – 2 h. Co-administration of a decarboxylase inhibitor (e.g. carbidopa, benserazide) doubles the half-life of 5-HTP to ≈ 3 – 4 h,[36][15] and enhances exposure several-fold, depending on the dosing regimen.[15][37]
Metabolism
5-HTP is
5-HTP | AAAD | Serotonin | |
PLP | |||
Pharmacology
The psychoactive action of 5-HTP is derived from its increase in production of serotonin in central nervous system tissue.[43]
Research shows that co-administration with carbidopa greatly increases plasma 5-HTP levels.[44] Other studies have indicated the risk of a scleroderma-like condition resulting from the combination of 5-HTP and carbidopa.[45]
Regulatory status
There are currently no approved drug products containing 5-HTP approved by the
As of 25 August 2020, Hungary added 5-HTP to the controlled psychoactive substances list, prohibiting production, sale, import, storage and use, becoming the first country to do so.[48]
5-HTP slow-release
5-HTP's short half-life is impractical for chronic drug therapy. Research conducted at Duke University in mice have demonstrated that 5-HTP when administered as slow-release appears to gain drug properties.[49] Slow-release delivery attenuates or abolishes the peaks and valleys in 5-HTP exposure during treatment.[50] Slow-release delivery of 5-HTP markedly improved the safety profile of 5-HTP and conferred stable plasma exposure of 5-HTP and strong and sustained enhancement of brain serotonin function.[49] This discovery indicates that 5-HTP slow-release medications represent a new avenue for treatment of brain disorders responsive to serotonergic enhancement.
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 all unfractionated foods, with lower total amino acid content correlating with increased tryptophan absorption.[51]
The seeds of the Griffonia simplicifolia, a climbing shrub native to West Africa and Central Africa, are used as an herbal supplement for their 5-HTP content.[52][53][54] In one 2010 trial, Griffonia simplicifolia extract appeared to increase satiety in overweight women.[55]
See also
- Cardiac fibrosis
- Melatonin
- N-Acetylserotonin
- Selective serotonin reuptake inhibitor
- Serotonin
- Tryptophan
References
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