World Library  
Flag as Inappropriate
Email this Article


Article Id: WHEBN0000564858
Reproduction Date:

Title: Pyridoxamine  
Author: World Heritage Encyclopedia
Language: English
Subject: B vitamins, Clorgiline, Vitamin B6, D-161, Sercloremine
Collection: Alcohols, B Vitamins, Dietary Supplements, Hydroxyarenes, Pyridines
Publisher: World Heritage Encyclopedia


IUPAC name
ChemSpider  Y
Jmol-3D images Image
Molar mass 168.20 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
 Y  (: Y/N?)

Pyridoxamine is one form of vitamin B6. Chemically it 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. The phenol at position 3 and aminomethyl group at position 4 of its ring endow pyridoxamine with a variety of chemical properties, including the scavenging of free radical species and carbonyl species formed in sugar and lipid degradation and chelation of metal ions that catalyze Amadori reactions.[1]


  • Research 1
  • FDA Regulatory Activity 2
  • Patenting Activity 3
  • See also 4
  • References 5
  • External links 6


Pyridoxamine can form fairly weak complexes with a number of transition metal ions, with a preference for Cu2+ and Fe3+.[2] The 3'-hydroxyl group of pyridoxamine allows for efficient hydroxyl radical scavenging.[2]

Pyridoxamine inhibits the Maillard reaction and can block the formation of advanced glycation endproducts,[3] which are associated with medical complications of diabetes.[4] 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.[5] One research study found that pyridoxamine specifically reacts with the carbonyl group in Amadori products, but inhibition of post-Amadori reactions (that can lead to advanced glycation endproducts) is due in much greater part to the metal chelation effects of pyridoxamine.[1]

A variety of preclinical studies in animal models of diabetes indicated that pyridoxamine improved kidney histology comparable or superior to aminoguanidine.[5] Because of these results, pyridoxamine has been investigated for clinical utility in the treatment of diabetic nephropathy.[5][6]

Pyridoxamine also inhibits the formation of advanced lipoxidation endproducts during lipid peroxidation reactions by reaction with dicarbonyl intermediates.[7] In other preclinical research, pyridoxamine may be efficacious in treating diabetic neuropathy and retinopathy associated with diabetes[5][7] and kidney stone disease.[2] In one study, pyridoxamine was more effective at protecting from ionizing radiation-induced gastrointestinal epithelial apoptosis than amifostine (the only radioprotector currently Food and Drug Administration (FDA)-approved) due to pyridoxamine reactive oxygen species and reactive carbonyl species scavenging profile.[8]

FDA Regulatory Activity

Pyridoxamine was 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.[9][10][11][12]

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.[10] However, in 2005 Biostratum ran out of money and so was unable to begin a Phase III trial.[10] Investors in Biostratum had realized that because Biostratum had no patent on pyridoxamine itself, and that pyridoxamine was commonly available for purchase as a dietary supplement, the company would be unable to charge enough money for the treatment (should it be approved as a prescription drug by the FDA) for the investors to get a reasonable return on the investment they had already made (about $100M) much less on the additional investment a Phase III trial would require.[10] To solve this problem, Biostratum submitted a Citizen Petition to the FDA on July 29, 2005, seeking to disallow sales of pyridoxamine-containing supplements on the grounds that pyridoxamine, as the subject of an Investigational New Drug Application with the FDA, is a drug and not a dietary supplement.[10] This petition was opposed by the Council for Responsible Nutrition, a trade association of the dietary supplement industry.[10]

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.[11] 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."[13]

In 2006, Biostratum licensed its rights in Pyridorin to another company, NephroGenex [14] In 2008, NephroGenex restarted the clinical development of Pyridorin, which as of 2012 is still ongoing.[15]

Patenting Activity

A patent application claiming pharmaceutical compositions of pyridoxamine, and methods to use pyridoxamine to treat diabetic complications, was filed by Biostratum and was published in 2004.[16] The application does not claim pyridoxamine itself.

See also


  1. ^ a b Adrover M, Vilanova B, Frau J, Muñoz F, Donoso J (May 2008). "The pyridoxamine action on Amadori compounds: A reexamination of its scavenging capacity and chelating effect". Bioorg. Med. Chem. 16 (10): 5557–69.  
  2. ^ 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.  
  3. ^ Voziyan PA, Hudson BG (2005). "Pyridoxamine: the many virtues of a maillard reaction inhibitor". Ann. N. Y. Acad. Sci. 1043 (1): 807–16.  
  4. ^ Ahmed N, Thornalley PJ (2007). "Advanced glycation endproducts: what is their relevance to diabetic complications?". Diabetes Obes Metab 9 (3): 233–45.  
  5. ^ a b c d Giannoukakis N (2005). "Pyridoxamine (BioStratum)" (PDF). Curr Opin Investig Drugs 6 (4): 410–8.  
  6. ^ 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.  
  7. ^ 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.  
  8. ^ Thotala D, Chetyrkin S, Hudson B, Hallahan D, Voziyan P, Yazlovitskaya E (September 2009). "Pyridoxamine protects intestinal epithelium from ionizing radiation-induced apoptosis". Free Radic. Biol. Med. 47 (6): 779–85.  
  9. ^ "FDA finds vitamin B6 form not legal in supplements",, February 2, 2009
  10. ^ a b c d e f "Big problem for BioStratum", Triangle Business Journal, October 14, 2005
  11. ^ a b "FDA's pyridoxamine decision: FDA's decision regarding pyridoxamine has larger implications for dietary ingredients in general", Entrepreneur, April, 2009
  12. ^!documentDetail;D=FDA-2005-P-0259-0004
  13. ^ FDA-2005-P-0259-0004: FDA Response to Biostratum, Inc. (Kathleen M Sanzo, Esq) - Petition Partial Approved and Denial
  14. ^
  15. ^
  16. ^ (WO/2004/112788) PYRIDOXAMINE FOR THE TREATMENT OF DIABETIC KIDNEY DISEASE, World Intellectual Property Organization

External links

  • Clinical trials testing Pyridoxamine (
    • Effect of Pyridorin in Patients With Diabetic Nephropathy (NCT00320060)
    • Effect of Pyridorin in Patients With Diabetic Nephropathy (NCT00320021)
    • Safety and Efficacy Study of Pyridorin in Patients With Nephropathy Due to Type 2 Diabetes (NCT00734253)
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.

Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.