Absorption, Distribution and Excretion
The dosage of (L)-tryptophan and vegetable oil soft capsules is lower than that of conventional dosage forms. Serum free tryptophan concentrations peak within 1 hour of administration, compared to 4-5 times the dose required for tablets or hard capsules. Absorption and Metabolism Tryptophan is readily absorbed from the gastrointestinal tract. It binds extensively to serum albumin. It is metabolized to serotonin and other metabolites, including kynurenine derivatives, and excreted in urine. Pyridoxine and ascorbic acid appear to be involved in its metabolism. Although free amino acids dissolved in body fluids constitute only a small fraction of the total amino acids in the body, they are essential for maintaining the nutrition and metabolism of proteins in the human body. While plasma is the most readily available sampling site, most amino acids are found in higher concentrations in intracellular pools. Typically, large neutral amino acids like leucine and phenylalanine are in near-equilibrium with their plasma concentrations. However, some other amino acids, particularly glutamine, glutamate, and glycine, are 10 to 50 times higher in intracellular pools than in plasma. Dietary changes or pathological conditions can lead to significant alterations in the concentrations of various free amino acids in plasma and tissue pools. /Amino Acids/
After ingestion, proteins denature under the influence of gastric acid and are hydrolyzed into smaller peptides by pepsin. The activity of pepsin increases with the increase in gastric acid after eating. Subsequently, proteins and peptides enter the small intestine, where peptide bonds are hydrolyzed by various enzymes. These specific enzymes originate from the pancreas and include trypsin, chymotrypsin, elastase, and carboxypeptidase. The resulting mixture of free amino acids and small peptides is then transported to mucosal cells via various carrier systems, each targeting specific amino acids, dipeptides, and tripeptides, with each system being specific to a limited range of peptide substrates. After intracellular hydrolysis of absorbed peptides, free amino acids are subsequently secreted into the portal vein bloodstream via other specific carrier systems within the mucosal cells, or further metabolized intracellularly. Absorbed amino acids enter the liver, where some are absorbed and utilized; the remainder enters the systemic circulation and is utilized by peripheral tissues. /Amino Acids/
For more complete data on the absorption, distribution, and excretion of (L)-tryptophan (9 in total), please visit the HSDB record page.

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Metabolism/Metabolites
Hepatic metabolism.
In Hartnap disease…due to defects in the renal and intestinal absorption of tryptophan, it appears in the urine…it is an intermediate metabolite in the synthesis of serotonin (5-hydroxytryptamine) and 5-hydroxyindoleacetic acid (HIAA).
In bladder cancer patients, after ingesting a loading dose of L-tryptophan, the excretion of kynurenic acid, acetylenin, kynurenine, and 3-hydroxykynurenine was significantly higher than in controls without known disease.
Tryptophan is metabolized in the liver. Tryptophan pyrrolase and tryptophan hydroxylase. Metabolites include serotonin (which can be converted to serotonin) and kynurenine derivatives. Some tryptophan is converted to nicotinic acid and nicotinamide. Pyridoxine and ascorbic acid are cofactors for tryptophan decarboxylation and hydroxylation, respectively; pyridoxine appears to prevent the accumulation of kynurenine metabolites. In humans, it produces indole-3-pyruvate… In rats, it produces tryptophan; in guinea pigs, it produces tryptophan. /Excerpt from table/
For more complete data on (L)-tryptophan (21 in total), please visit the HSDB record page.
Liver.

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Biological half-life
The biological half-life of tryptophan is reported to be 15.8 hours.

Toxicity Summary
Tryptophan undergoes several important side reactions during its catabolism to acetoacetic acid. The first enzyme in this catabolism pathway is porphyrin oxygenase, which opens the indole ring. This enzyme is highly inducible, with its concentration increasing nearly tenfold under a high-tryptophan diet. Kyrenin is the first key branching intermediate in this pathway. Kyrenin undergoes deamination in the standard transamination reaction to produce kyrenuric acid. Kyrenuric acid and its metabolites have been shown to have anti-excitatory toxicity and anticonvulsant effects. The second branching reaction produces anthranilic acid and alanine. Further downstream of the main catabolism pathway, another equal amount of alanine is produced; it is the production of these alanine residues that allows tryptophan to be classified as a glucogenic and ketogenic amino acid. The second important branching point converts kyrenin to 2-amino-3-carboxymethaneconic acid semialdehyde, which has two metabolic pathways. Carbon flows primarily from this intermediate to glutaric acid. A significant side effect in the liver is transamination and multiple rearrangements, producing small amounts of niacin, which in turn generates small amounts of NAD+ and NADP+. Interactions: Acetylsalicylic acid can reduce the protein binding rate of tryptophan in human serum, leading to elevated serum free tryptophan levels. Metabolic patterns also change, with increased urinary excretion of xanthuric acid and 3-hydroxykynurenine, while the excretion of 3-hydroxyanthranilic acid decreases. Although tryptophan is believed to improve the clinical efficacy of monoamine oxidase inhibitors (MAOIs), it should be noted that its adverse effects may also be enhanced. Concomitant use of tryptophan with drugs that inhibit serotonin reuptake may exacerbate the latter's adverse effects and induce serotonin syndrome. There are reports of sexual dysfunction in patients taking tryptophan concurrently with phenothiazines or benzodiazepines. For more complete data on interactions of (L)-tryptophan (16 in total), please visit the HSDB record page.

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Non-human toxicity values
Rat intraperitoneal LD50: 1634 mg/kg
Mouse intraperitoneal LD50: 4800 mg/kg

[1]. L-Tryptophan activates the aryl hydrocarbon receptor and induces cell cycle arrest in porcine trophectoderm cells. Theriogenology. 2021 Sep 1:171:137-146.

[2]. Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo. Materials (Basel). 2021 Jan 4;14(1):208.

[3]. Conversion of L-tryptophan to serotonin and melatonin in human melanoma cells. FEBS Lett. 2002 Jan 30;511(1-3):102-6.

Therapeutic Uses
Tryptophan is a precursor to serotonin. Since serotonin depletion in the central nervous system is associated with depression, tryptophan has been used to treat depression. Although tryptophan has been used alone, evidence of its efficacy is insufficient, so it is often used as an adjunct therapy for depression. Sometimes, tryptophan is used in combination with pyridoxine and ascorbic acid, both of which are involved in the metabolism of tryptophan to serotonin.
/Experimental Uses/: Administration of L-tryptophan inhibited Walker 256 intramuscular cancer in rats.
(L)-tryptophan shortened sleep latency and slightly prolonged sleep duration in normal subjects without altering the qualitative characteristics of polysomnography during sleep.
In patients with insomnia, L-tryptophan prolonged sleep duration, shortened sleep latency, and reduced the number of awakenings.
Beneficial effects were observed after treatment with L-tryptophan in two patients with myoclonus. In each case, a suspension containing 1 gram of (L)-tryptophan/15 mL of methylcellulose and water was prepared and administered orally at a dose of 10 grams daily divided into 5 doses. For more complete data on the therapeutic uses of (L)-tryptophan (11 in total), please visit the HSDB record page. Drug Warnings Oral L-tryptophan has been used to increase serotonin levels in the brain because serotonin plays a role in inducing and maintaining sleep. While a 1-gram dose of L-tryptophan significantly shortens sleep latency and total wakefulness without altering sleep patterns, its hypnotic effect occurs only in the early stages of the sleep cycle and is difficult to predict, with a less than ideal dose-response relationship. Because its hypnotic effect has not been confirmed in other studies, this use of L-tryptophan should be considered an investigational use and is not recommended for routine clinical practice. To avoid central serotonin toxicity, tryptophan should not be used in patients taking monoamine oxidase inhibitors or the serotonin reuptake inhibitor fluoxetine (Prozac).
Products containing tryptophan are associated with eosinophilic-myalgia syndrome. Other reported adverse reactions include nausea, headache, dizziness, and drowsiness.
There have been reports of increased bladder tumor incidence in mice after oral administration of L-tryptophan and after implantation of cholesterol particles into the bladder cavity. However, no increase in tumor incidence was observed with oral administration of high doses of tryptophan alone.
Tryptophan is associated with eosinophilic-myalgia syndrome; caution is advised for patients who experience some (but not all) symptoms of this syndrome after taking this medication. This product should not be used in patients with a history of eosinophilic-myalgia syndrome, which is associated with tryptophan treatment.
For more complete data on drug warnings for (L)-tryptophan (7 of 7), please visit the HSDB record page.

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Pharmacodynamics
Tryptophan is essential for the production of proteins, enzymes, and muscle tissue in the human body. It is also necessary for the production of niacin and the synthesis of the neurotransmitters serotonin and melatonin. Tryptophan supplements can be used as a natural relaxant to help relieve insomnia. Tryptophan can also reduce anxiety and depression and has been shown to reduce the intensity of migraines. Other promising indications include relieving chronic pain, reducing impulsivity or mania, and treating obsessive-compulsive disorder. Tryptophan also appears to help the immune system and may reduce the risk of heart spasms. Tryptophan deficiency may lead to coronary artery spasms. Tryptophan is an essential nutrient in infant formula and intravenous infusions. For patients who do not respond well to conventional antidepressants, tryptophan is also marketed as a prescription drug (tryptophan tablets). It is also used to treat seasonal affective disorder (winter-onset depression). Tryptophan is a precursor to the synthesis of serotonin (5-hydroxytryptamine, 5-HT) and melatonin (N-acetyl-5-methoxytryptamine).

C11H12N2O2

204.22

204.089

73-22-3

27813-82-7

6305

White to off-white solid powder

1.4±0.1 g/cm3

447.9±35.0 °C at 760 mmHg

289-290 °C (dec.)(lit.)

224.7±25.9 °C

0.0±1.1 mmHg at 25°C

1.698

1.04

3

3

3

15

245

1

C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)N

QIVBCDIJIAJPQS-VIFPVBQESA-N

InChI=1S/C11H12N2O2/c12-9(11(14)15)5-7-6-13-10-4-2-1-3-8(7)10/h1-4,6,9,13H,5,12H2,(H,14,15)/t9-/m0/s1

(2S)-2-amino-3-(1H-indol-3-yl)propanoic acid

NSC-13119 NSC 13119 Tryptophan

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~7.69 mg/mL (~37.65 mM)
H2O : ~5 mg/mL (~24.48 mM)

Solubility in Formulation 1: ≥ 0.77 mg/mL (3.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 0.77 mg/mL (3.77 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 0.77 mg/mL (3.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 6.25 mg/mL (30.60 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

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Solubility in Formulation 5: 20 mg/mL (97.93 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; Need ultrasonic and warming and heat to 45°C.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)