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Pyridoxamine
Identifiers
CAS number 85-87-0 Yes check.svgY
PubChem 1052
ChemSpider 1023
SMILES
Properties
Molecular formula C8H12N2O2
Molar mass 168.19 g mol−1
 Yes check.svgY (what is this?)  (verify)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Pyridoxamine is a vitamer in the vitamin B6 family, which includes pyridoxal and pyridoxine. Pyridoxamine is converted to the biologically active form, pyridoxal 5-phosphate, via the by vitamin B6 salvage pathway,[1] which acts as an enzyme cofactor in a variety of metabolic processes. In food, pyridoxamine is commonly found as a 5’-phosphate derivative, which is hydrolyzed by intestinal phosphatases to pyridoxamine and absorbed in the jejunum.[2] Absorbed pyridoxamine is converted to pyridoxamine 5’-phosphate by pyridoxal kinase, which is further converted to the active pyridoxal 5-phosphate by pyridoxamine-phosphate transaminase or pyridoxine 5’-phosphate oxidase.[3]

Pyridoxamine is based on a pyridine ring structure, with hydroxyl, methyl, aminomethyl, and hydroxymethyl substituents. It differs from pyridoxine by the substituent at the 4-position.

Contents

Research

Pyridoxamine can form farily weak complexes with a number of transition metal ions, with a preference for Cu2+ and Fe3+.[4] The 3'-hydroxyl group of pyridoxamine allows for efficient hydroxyl radical scavenging.[4]

Pyridoxamine inhibits the Maillard reaction and can block the formation of advanced glycation endproducts,[5] which are associated with medical complications of diabetes.[6] Pyridoxamine is hypothesized to trap intermediates in the formation of Amadori products released from glycated proteins, possibly preventing the breakdown of glycated proteins by disrupting the catalysis of this process through disruptive interactions with the metal ions crucial to the redox reaction.[7]

A variety of preclinical studies in animal models of diabetes indicated that pyridoxamine improved kidney histology comparable or superior to aminoguanidine.[7] Because of these results, pyridoxamine has been investigated for clinical utility in the treatment of diabetic nephropathy.[7][8]

Pyridoxamine also inhibits the formation of advanced lipoxidation endproducts during lipid peroxidation reactions by reaction with dicarbonyl intermediates.[9] In other preclinical research, pyridoxamine may be efficacious in treating diabetic neuropathy and retinopathy associated with diabetes[7][9] and kidney stone disease.[4]

Patent controversy

Pyridoxamine is marketed as a dietary supplement, often as the hydrochloride salt, pyridoxamine dihydrochloride. However, in the United States, the FDA ruled in January 2009 that pyridoxamine must be regulated as a pharmaceutical drug because it is the active ingredient in Pyridorin, a drug designed by Biostratum, Inc., to prevent the progression of diabetic nephropathy.[10][11][12]

A patent for Pyridorin, from an application by Biostratum, was published in 2004.[13] Pyridorin had success in early clinical trials, found to be effective in slowing the progression of diabetic neuropathy in a phase II trial on 224 patients.[11] However, the clinical trial progression of Pyridorin was stalled when it was determined that the active ingredient (pyridoxamine) was commonly available for purchase on the Internet.[11] As the subject of an Investigational New Drug Application with the FDA, Biostratum submitted a Citizen Petition to the FDA on July 29, 2005, seeking to disallow sales of pyridoxamine-containing supplements.[11] This petition was opposed by the Council for Responsible Nutrition, a trade association of the dietary supplement industry.[11] On January 12, 2009, the FDA ruled that products containing pyridoxamine are excluded from the definition of dietary supplements as defined by the Dietary Supplement Health and Education Act of 1994.[12] The FDA stated that the status of Pyridorin as an investigational new drug, as a result of an application filed by BioStratum in July 1999 and effective on September 1, 1999, meant that "the marketing of pyridoxamine in a dietary supplement is essentially equivalent to the marketing of an investigational new drug as a dietary supplement" because there was an "absence of independent, verifiable evidence that the substance was marketed as a food or a dietary supplement prior to its authorization for investigation as a new drug."[14]

See also

References

  1. ^ Roje S (2007). "Vitamin B biosynthesis in plants". Phytochemistry 68 (14): 1904–21. doi:10.1016/j.phytochem.2007.03.038. PMID 17512961. 
  2. ^ Merrill AH, Henderson JM (1990). "Vitamin B6 metabolism by human liver". Ann. N. Y. Acad. Sci. 585: 110–7. doi:10.1111/j.1749-6632.1990.tb28047.x. PMID 2192606. 
  3. ^ Ink SL, Henderson LM (1984). "Vitamin B6 metabolism". Annu. Rev. Nutr. 4: 455–70. doi:10.1146/annurev.nu.04.070184.002323. PMID 6380540. 
  4. ^ a b c Voziyan PA, Hudson BG (2005). "Pyridoxamine as a multifunctional pharmaceutical: targeting pathogenic glycation and oxidative damage". Cell. Mol. Life Sci. 62 (15): 1671–81. doi:10.1007/s00018-005-5082-7. PMID 15905958. 
  5. ^ Voziyan PA, Hudson BG (2005). "Pyridoxamine: the many virtues of a maillard reaction inhibitor". Ann. N. Y. Acad. Sci. 1043: 807–16. doi:10.1196/annals.1333.093. PMID 16037308. 
  6. ^ Ahmed N, Thornalley PJ (2007). "Advanced glycation endproducts: what is their relevance to diabetic complications?". Diabetes Obes Metab 9 (3): 233–45. doi:10.1111/j.1463-1326.2006.00595.x. PMID 17391149. 
  7. ^ a b c d Giannoukakis N (2005). "Pyridoxamine (BioStratum)". Curr Opin Investig Drugs 6 (4): 410–8. PMID 15898348. http://www.biomedcentral.com/content/pdf/cd-592993.pdf. 
  8. ^ Williams ME, Bolton WK, Khalifah RG, Degenhardt TP, Schotzinger RJ, McGill JB (2007). "Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy". Am. J. Nephrol. 27 (6): 605–14. doi:10.1159/000108104. PMID 17823506. 
  9. ^ a b Metz TO, Alderson NL, Thorpe SR, Baynes JW (2003). "Pyridoxamine, an inhibitor of advanced glycation and lipoxidation reactions: a novel therapy for treatment of diabetic complications". Arch. Biochem. Biophys. 419 (1): 41–9. doi:10.1016/j.abb.2003.08.021. PMID 14568007. 
  10. ^ "FDA finds vitamin B6 form not legal in supplements", newsfood.com, February 2, 2009
  11. ^ a b c d e "Big problem for BioStratum", Triangle Business Journal, October 14, 2005
  12. ^ a b "FDA's pyridoxamine decision: FDA's decision regarding pyridoxamine has larger implications for dietary ingredients in general", Entrepreneur, April, 2009
  13. ^ (WO/2004/112788) PYRIDOXAMINE FOR THE TREATMENT OF DIABETIC KIDNEY DISEASE, World Intellectual Property Organization
  14. ^ FDA-2005-P-0259-0004: FDA Response to Biostratum, Inc. (Kathleen M Sanzo, Esq) - Petition Partial Approved and Denial

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