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Chemical Compound Review

Metadoxil     4,5-bis(hydroxymethyl)-2- methyl-pyridin-3...

Synonyms: Metasin, Metadoxine, Metadoxil (TN), AG-G-96419, STOCK6S-68822, ...
 
 
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Disease relevance of Metadoxine

 

High impact information on Metadoxine

  • Long-term ethanol administration enhances age-dependent modulation of redox state in central and peripheral organs of rat: protection by metadoxine [4].
  • In the present study, we examined the effect of metadoxine on striatal levels of dopamine, 5-hydroxytryptamine (5-HT) and their metabolites in male C57 Black mice [5].
  • The effects of metadoxine (pyrrolidone-carboxylic acid; PCA) and pyridoxine on the locomotor responses to ethanol in mice were compared [6].
  • ABSTRACT: BACKGROUND: We carried out a three months follow-up study on the efficacy of metadoxine in a cohort of alcoholics admitted to the Alcohol misuse Long-term Treatment (ALT) Unit - University of Pisa (Italy) [7].
  • Metadoxine was subjected to acid, alkali and neutral hydrolysis, oxidation, dry and wet heat treatment and photo and UV degradation [8].
 

Anatomical context of Metadoxine

  • In the present work we have investigated the effect of metadoxine on some parameters of cellular damage in hepatocytes and hepatic stellate cells in culture treated with ethanol and acetaldehyde [9].
  • BACKGROUND/AIMS: To evaluate liver-beneficial properties of metadoxine, not related with alcohol metabolism, bioactivation of external toxins or antioxidant mechanisms, the chronic bile duct ligation (BDL) model was used and results were compared with colchicine [10].
 

Associations of Metadoxine with other chemical compounds

 

Gene context of Metadoxine

  • At concentrations higher than 0.1 mM, metadoxine inhibits rat class II alcohol dehydrogenase, although this would probably not affect the physiological ethanol metabolism [12].
  • Thus, metadoxine could be useful in preventing the damage produced in early stages of alcoholic liver disease as it prevents the redox imbalance of the hepatocytes and prevents TNF- alpha induction, one of the earliest events in hepatic damage [9].
  • There were striking increases in fibronectin and pro-alpha 2(I)collagen mRNA contents in the livers of CCL4-treated animals and these enhancements were less evident in the metadoxine-treated rats [3].
 

Analytical, diagnostic and therapeutic context of Metadoxine

  • After treatment, the percentage of patients with ultrasonographic signs of steatosis was significantly lower in the metadoxine group (28% vs 70%, p < 0.01) and the degree of steatosis was also lower in this group [2].
  • CONCLUSIONS: In patients with alcoholic fatty liver, metadoxine accelerates the normalization of liver function tests and the ultrasonographic changes, even in those who do not completely abstain from alcohol intake [2].

References

  1. Treatment of alcoholic fatty liver: is the metabolic effect of metadoxine the only reason for improved liver function? Stefanini, G.F., Addolorato, G., Caputo, F., Bernardi, M., Gasbarrini, G. J. Hepatol. (1999) [Pubmed]
  2. Metadoxine accelerates fatty liver recovery in alcoholic patients: results of a randomized double-blind, placebo-control trial. Spanish Group for the Study of Alcoholic Fatty Liver. Caballería, J., Parés, A., Brú, C., Mercader, J., García Plaza, A., Caballería, L., Clemente, G., Rodrigo, L., Rodés, J. J. Hepatol. (1998) [Pubmed]
  3. Changes in expression of the albumin, fibronectin and type I procollagen genes in CCl4-induced liver fibrosis: effect of pyridoxol L,2-pyrrolidon-5 carboxylate. Arosio, B., Santambrogio, D., Gagliano, N., Annoni, G. Pharmacol. Toxicol. (1993) [Pubmed]
  4. Long-term ethanol administration enhances age-dependent modulation of redox state in central and peripheral organs of rat: protection by metadoxine. Calabrese, V., Randazzo, G., Ragusa, N., Rizza, V. Drugs under experimental and clinical research. (1998) [Pubmed]
  5. Effect of metadoxine on striatal dopamine levels in C57 black mice. Fornai, F., Grazia Alessandrì, M., Bonuccelli, U., Scalori, V., Corsini, G.U. J. Pharm. Pharmacol. (1993) [Pubmed]
  6. Metadoxine (pyrrolidone carboxylate of pyridoxine) antagonizes the locomotor-stimulatory effect of ethanol in mice. Garau, B., Fadda, F., Melis, F., Gelso, E., Gessa, G.L. Alcohol Alcohol. (1992) [Pubmed]
  7. A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence. Guerrini, I., Gentili, C., Nelli, G., Guazzelli, M. Substance abuse treatment, prevention, and policy (2006) [Pubmed]
  8. Application of stability-indicating HPTLC method for quantitative determination of metadoxine in pharmaceutical dosage form. Kaul, N., Agrawal, H., Patil, B., Kakad, A., Dhaneshwar, S.R. Farmaco (2005) [Pubmed]
  9. Metadoxine prevents damage produced by ethanol and acetaldehyde in hepatocyte and hepatic stellate cells in culture. Gutiérrez-Ruiz, M.C., Bucio, L., Correa, A., Souza, V., Hernández, E., Gómez-Quiroz, L.E., Kershenobich, D. Pharmacol. Res. (2001) [Pubmed]
  10. Fibrosis and glycogen stores depletion induced by prolonged biliary obstruction in the rat are ameliorated by metadoxine. Muriel, P., Deheza, R. Liver Int. (2003) [Pubmed]
  11. Alcoholic abstinence syndrome: short-term treatment with metadoxine. Bono, G., Sinforiani, E., Merlo, P., Belloni, G., Soldati, M., Gelso, E. International journal of clinical pharmacology research. (1991) [Pubmed]
  12. Action of metadoxine on isolated human and rat alcohol and aldehyde dehydrogenases. Effect on enzymes in chronic ethanol-fed rats. Parés, X., Moreno, A., Peralba, J.M., Font, M., Bruseghini, L., Esteras, A. Methods and findings in experimental and clinical pharmacology. (1991) [Pubmed]
 
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