| Size | Price | Stock | Qty |
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| 500mg |
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| Other Sizes |
| Targets |
Metadoxine targets multiple biochemical pathways. In HepG2 cells, it prevents glutathione depletion and inhibits the increase in lipid peroxidation induced by ethanol and its metabolite acetaldehyde. In hepatic stellate cells, it prevents acetaldehyde‑induced collagen accumulation and attenuates TNF‑α secretion. Additionally, it blocks adipocyte differentiation by inhibiting the protein kinase A‑cAMP response element‑binding protein (PKA‑CREB) pathway. Its primary protective effects are mediated through antioxidant, anti‑inflammatory, and anti‑fibrotic mechanisms in the liver.
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| ln Vitro |
Simultaneous metadoxine therapy greatly suppressed adipogenic differentiation in a dose-dependent manner. Metadoxine therapy from day 4 to day 8 is essential to suppress MDI-induced preadipocyte differentiation [1]. Metadoxine reduces glutathione depletion and the increase in ethanol- and acetaldehyde-induced lipid peroxidative damage in HepG2 cells. In hepatic stellate cells, metadoxine inhibits the acetaldehyde-induced increase in collagen and the reduction of TNF-α release. Therefore, metadoxine may be utilized to prevent early damage in alcoholic liver disease, as it avoids redox imbalance in hepatocytes and prevents TNF-α production, one of the earliest events in liver damage [2].
In vitro, Metadoxine has been shown to protect HepG2 cells against ethanol‑ and acetaldehyde‑induced toxicity by maintaining intracellular glutathione levels and reducing malondialdehyde (MDA) formation, a marker of lipid peroxidation. In cultured hepatic stellate cells (HSC‑T6), it decreases collagen type I and III synthesis and reduces acetaldehyde‑stimulated TNF‑α release. Furthermore, in 3T3‑L1 preadipocytes, it inhibits adipocyte differentiation and lipid accumulation via suppression of the PKA‑CREB pathway. These activities underlie its hepatoprotective and anti‑steatotic effects. |
| ln Vivo |
In vivo, Metadoxine is clinically used for the treatment of acute and chronic alcohol intoxication and alcoholic liver disease. It accelerates the elimination of ethanol from blood and tissues, reduces hepatic fat accumulation, and improves liver function parameters (e.g., ALT, AST, GGT). It also alleviates psychological symptoms such as anxiety and depression associated with alcohol withdrawal. In animal models, it attenuates ethanol‑induced hepatic steatosis, inflammation, and fibrosis, and normalizes redox balance. Clinical studies have shown significant improvements in liver histology and biochemistry in patients with ALD.
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| Enzyme Assay |
In vitro enzyme assays for Metadoxine are not typically performed on a single enzyme, as it acts through multiple mechanisms. However, its effects on oxidative stress can be assessed by measuring glutathione (GSH) levels using the DTNB‑GSSG reductase recycling assay, and lipid peroxidation by the thiobarbituric acid reactive substances (TBARS) assay in hepatocyte cultures. Anti‑fibrotic activity is evaluated by measuring collagen content (hydroxyproline assay) and pro‑inflammatory cytokines (TNF‑α, IL‑6) by ELISA in hepatic stellate cells treated with acetaldehyde.
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| Cell Assay |
In vitro cellular assays for Metadoxine are performed using human HepG2 hepatocytes, rat hepatic stellate cells (HSC‑T6), or mouse 3T3‑L1 preadipocytes. Cells are exposed to ethanol (50‑100 mM) or acetaldehyde (100‑500 µM) in the presence of Metadoxine (0.1‑10 mM) for 24‑48 hours. Viability is measured by MTT, and intracellular ROS by DCFH‑DA. GSH, MDA, and cytokine levels are quantified by colorimetric or ELISA methods. For adipogenesis, 3T3‑L1 cells are differentiated with insulin, dexamethasone, and IBMX, and lipid accumulation is assessed by Oil Red O staining.
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| Animal Protocol |
In vivo animal studies for Metadoxine are conducted in rodent models of ethanol‑induced liver injury. Male Wistar rats or C57BL/6 mice are administered ethanol (e.g., 5 g/kg/day, intragastrically) for 4‑12 weeks to induce steatohepatitis. Metadoxine is given orally (e.g., 100‑300 mg/kg/day) concurrently. Endpoints include serum ALT, AST, and GGT; hepatic triglyceride and cholesterol content; histopathology (H&E, Oil Red O, Masson's trichrome); and hepatic GSH, MDA, TNF‑α, and collagen levels. Behavioral tests (open field, elevated plus maze) may assess alcohol‑related neuropsychological effects.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies in humans and animals show that Metadoxine is rapidly absorbed after oral administration, with peak plasma concentrations reached within 1‑2 hours. It is distributed to the liver and other tissues. The half‑life is approximately 2‑4 hours. It is metabolized to pyridoxal and pyrrolidone carboxylate, which are excreted in urine. No significant accumulation occurs with repeated dosing. Bioavailability is about 80‑90%. Its pharmacokinetic profile supports twice‑daily dosing in clinical settings.
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| Toxicity/Toxicokinetics |
Metadoxine is generally well‑tolerated in clinical use. Common adverse effects are mild and include gastrointestinal discomfort (nausea, diarrhea) and headache. Serious toxicity is rare. In animal studies, the LD₅₀ is high (>2000 mg/kg). It is contraindicated in patients with known hypersensitivity to pyridoxine or pyrrolidone derivatives. No significant hepatotoxicity or nephrotoxicity has been observed at therapeutic doses. Long‑term safety data are limited, but it has been used for decades in some European and Asian countries.
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| References | |
| Additional Infomation |
Metadoxine is an ion‑pair of pyridoxine and pyrrolidone carboxylate, used clinically for alcoholic liver disease and alcohol intoxication. It prevents GSH depletion, reduces lipid peroxidation, inhibits collagen deposition, and modulates PKA‑CREB signaling. It has a molecular weight of 298.29 and formula C₁₃H₁₈N₂O₆. It is approved in several countries (e.g., Italy, Russia, China) as a hepatoprotective agent, but not by the FDA. Its mechanism is multifactorial, involving antioxidant, anti‑inflammatory, and anti‑fibrotic actions.
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| Molecular Formula |
C8H11NO3.C5H7NO3
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| Molecular Weight |
298.3
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| Exact Mass |
298.116
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| CAS # |
74536-44-0
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| PubChem CID |
115198
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| Appearance |
White to off-white solid powder
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| Boiling Point |
491.9ºC at 760 mmHg
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| Melting Point |
102-104ºC
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| Flash Point |
251.3ºC
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
21
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| Complexity |
297
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=NC=C(C(=C1O)CO)CO.C1CC(=O)N[C@@H]1C(=O)O
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| InChi Key |
RYKKQQUKJJGFMN-HVDRVSQOSA-N
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| InChi Code |
InChI=1S/C8H11NO3.C5H7NO3/c1-5-8(12)7(4-11)6(3-10)2-9-5;7-4-2-1-3(6-4)5(8)9/h2,10-12H,3-4H2,1H3;3H,1-2H2,(H,6,7)(H,8,9)/t;3-/m.0/s1
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| Chemical Name |
4,5-bis(hydroxymethyl)-2-methylpyridin-3-ol;(2S)-5-oxopyrrolidine-2-carboxylic acid
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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. |
| 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) |
H2O : ≥ 155 mg/mL (~519.63 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (335.24 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3523 mL | 16.7616 mL | 33.5233 mL | |
| 5 mM | 0.6705 mL | 3.3523 mL | 6.7047 mL | |
| 10 mM | 0.3352 mL | 1.6762 mL | 3.3523 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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