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| Other Sizes |
| Targets |
- Thiamine nitrate (converted to active thiamine pyrophosphate, TPP, in vivo) acts as a coenzyme for thiamine-dependent enzymes, including pyruvate dehydrogenase complex (PDHC), α-ketoglutarate dehydrogenase complex (α-KGDHC), and transketolase (TK)[1]
- Thiamine nitrate interacts with the thiamine transporter Slc19a3 (deficient in Slc19a3-/- mice); high-dose Thiamine nitrate bypasses the defective Slc19a3 transporter to enter brain cells[2] |
|---|---|
| ln Vitro |
At 7 weeks, the blood thiamine levels of homozygous KO and KI mice fed a standard diet dropped to 0.058±0.051 and 0.126±0.092 μM, respectively, compared with WT mice (0.796±0.259 μM). Following a thiamine-restricted diet (thiamine: 0.60 mg/100 g of chow) for WT and homozygous KO and KI mice, blood thiamine concentrations were considerably lower on days 5 and 14, respectively, at 0.010 ± 0.009. and, in contrast to WT mice (0.609±0.288 μM), 0.010±0.006 μM. In WT mice given a typical diet, the brain homogenates had a thiamine concentration of 3.81±2.18 nmol/g wet weight, while KO and KI brain homogenates had thiamine values of 1.33±0.96 and 2.16±1.55 nmol/g wet weight, respectively. Notably, following 5 days (0.95±0.72 nmol/g wet weight) and 14 days (1.11±0.24) of eating a thiamine-restricted diet (thiamine: 0.60 mg/100 g food), the KO and KI were reduced. Prior to the mice displaying illness symptoms, thiamine concentrations in brain homogenates fell gradually in animals (nmol/g wet weight) as compared to WT (3.65 ± 1.02 nmol/g wet weight), respectively [2].
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| ln Vivo |
WT, homozygous and heterozygous KO and KI mice fed a conventional diet (thiamine: 1.71 mg/100 g) survived for more than 6 months without any disease phenotype. Homozygous KO and KI mice on a thiamine-restricted diet (thiamine: 0.60 mg/100 g of chow) displayed paralysis, weight loss, and immobility, respectively, and died after 12 and 30 days, respectively. Likewise, homozygous KO and KI mice fed a thiamine-restricted diet with a reduced thiamine percentage (thiamine: 0.27 mg/100 g of food) died within 14 and 18 days, respectively. Nevertheless, mice administered a thiamine-restricted diet (thiamine: 0.60 mg or 0.27 mg/100g of chow) in both WT and heterozygous KO and KI groups survived for over 6 months without exhibiting any signs of sickness [2].
- In patients with thiamine deficiency-induced delirium (e.g., alcohol-related Wernicke-Korsakoff syndrome, malnutrition), supplementation with Thiamine nitrate (parenteral or oral) reversed delirium symptoms. It restored cerebral thiamine levels, normalized the activity of PDHC and α-KGDHC in brain tissue, and improved cerebral energy metabolism (reduced lactate accumulation due to impaired glucose oxidation). [1] - In Slc19a3-deficient (Slc19a3-/-) mice (a model of hereditary thiamine-responsive encephalopathy), high-dose Thiamine nitrate (200 mg/kg/day, i.p.) significantly prolonged survival: median survival of untreated Slc19a3-/- mice was ~10 days after birth, while treated mice survived >60 days. It also prevented brain lesions: untreated mice developed vacuolar degeneration in the thalamus, brainstem, and cerebellum, whereas treated mice showed minimal to no pathological changes. Additionally, Thiamine nitrate increased brain TPP levels (by ~3-fold compared to untreated Slc19a3-/- mice) and restored PDHC activity in the brain. [2] |
| Enzyme Assay |
- Cerebral thiamine-dependent enzyme activity assay (for PDHC and α-KGDHC): Brain tissue (cortex, thalamus) from thiamine-deficient animals/patients was homogenized in ice-cold buffer containing Tris-HCl, EDTA, and dithiothreitol. The homogenate was centrifuged at 12,000 × g for 20 minutes at 4°C, and the supernatant was used as the enzyme source.
- PDHC activity: The reaction mixture included enzyme supernatant, pyruvate, coenzyme A, NAD+, and TPP (as a cofactor for positive control). The reaction was initiated by adding pyruvate, and the increase in absorbance at 340 nm (due to NADH production) was measured at 37°C for 10 minutes. Activity was calculated as nmol NADH generated per mg protein per minute. - α-KGDHC activity: The reaction mixture included enzyme supernatant, α-ketoglutarate, coenzyme A, NAD+, and TPP. The reaction was initiated by adding α-ketoglutarate, and absorbance at 340 nm was measured as above to quantify NADH production and calculate enzyme activity. [1] - Brain TPP level detection: Brain tissue from Slc19a3-/- mice was homogenized in perchloric acid (to extract thiamine derivatives) and neutralized with potassium hydroxide. TPP levels were measured by high-performance liquid chromatography (HPLC) with fluorescence detection (excitation: 375 nm, emission: 435 nm) using a TPP standard curve for quantification. [2] |
| Animal Protocol |
- Slc19a3-deficient mouse experiment:
1. Mouse model: Slc19a3-/- (homozygous) mice and wild-type (Slc19a3+/+) littermate controls (C57BL/6 background) were used, with experiments starting at postnatal day 1 (P1). 2. Thiamine nitrate administration: Treated group received Thiamine nitrate at 200 mg/kg/day via intraperitoneal injection (i.p.), once daily, from P1 until the end of the experiment (up to 60 days). Untreated group received equal volumes of sterile saline (i.p.) on the same schedule. 3. Observation and sampling: Mice were monitored daily for survival status and clinical signs (e.g., ataxia, lethargy). At the experimental endpoint or after natural death, mice were euthanized; brains were excised, half fixed in 4% paraformaldehyde (for histopathology) and half frozen at -80°C (for TPP measurement and enzyme activity assay). Histopathological analysis included paraffin embedding, sectioning (5 μm), HE staining, and light microscopy to assess brain lesions (vacuolar degeneration). [2] |
| References | |
| Additional Infomation |
3-((4-amino-2-methyl-5-pyrimidinyl)methyl)-5-(2-hydroxyethyl)-4-methylthiazole chloride.
- Thiamine nitrate is the nitrate form of thiamine (vitamin B1), a water-soluble vitamin. In the body, it is phosphorylated to TPP, the active coenzyme form, which is essential for carbohydrate metabolism and neurological function (e.g., neurotransmitter synthesis, maintaining the integrity of the blood-brain barrier). [1] - Thiamine deficiency can lead to brain energy depletion (due to impaired PDHC/α-KGDHC activity) and neuroinflammation, which in turn can cause delirium, especially in high-risk populations (alcoholics, malnourished elderly, postoperative patients). Thiamine nitrate supplementation is the first-line treatment for delirium caused by thiamine deficiency, and for severe cases, parenteral administration is preferred (the drug reaches the brain more quickly). [1] - Slc19a3 is a thiamine transporter expressed in the blood-brain barrier and brain parenchymal cells. Slc19a3 deficiency can lead to thiamine depletion in the brain and fatal encephalopathy. High doses of thiamine nitrate can overcome transporter deficiency through passive diffusion, making it a potential treatment for Slc19a3-related inherited thiamine-responsive disorders, such as thiamine-responsive megaloblastic anemia syndrome. [2] |
| Molecular Formula |
C12H17N5O4S
|
|---|---|
| Molecular Weight |
327.3595
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| Exact Mass |
327.1
|
| CAS # |
532-43-4
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| Related CAS # |
Thiamine monochloride;59-43-8;Thiamine hydrochloride;67-03-8
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| PubChem CID |
10762
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| Appearance |
White to off-white solid powder
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| Melting Point |
196-200°C
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| LogP |
1.473
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
22
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| Complexity |
287
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| Defined Atom Stereocenter Count |
0
|
| InChi Key |
UIERGBJEBXXIGO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H17N4OS.NO3/c1-8-11(3-4-17)18-7-16(8)6-10-5-14-9(2)15-12(10)13;2-1(3)4/h5,7,17H,3-4,6H2,1-2H3,(H2,13,14,15);/q+1;-1
|
| Chemical Name |
2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol;nitrate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~15 mg/mL (~45.82 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0547 mL | 15.2737 mL | 30.5474 mL | |
| 5 mM | 0.6109 mL | 3.0547 mL | 6.1095 mL | |
| 10 mM | 0.3055 mL | 1.5274 mL | 3.0547 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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