Deferoxamine

Deferoxamine
Names
IUPAC name
N'-{5-[Acetyl(hydroxy)amino]pentyl}-N-[5-({4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanoyl}amino)pentyl]-N-hydroxysuccinamide
Other names
N'-[5-(Acetyl-hydroxy-amino)pentyl]-N-[5-[3-(5-aminopentyl-hydroxy-carbamoyl) propanoylamino]pentyl]-N-hydroxy-butane diamide
Identifiers
70-51-9 YesY
2514118
ChEBI CHEBI:4356 YesY
ChEMBL ChEMBL556 YesY
ChemSpider 2867 YesY
DrugBank DB00746 YesY
Jmol interactive 3D Image
Image
KEGG D03670 YesY
PubChem 2973
UNII J06Y7MXW4D YesY
Properties
C25H48N6O8
Molar mass 560.69 g·mol−1
log P −0.614
Acidity (pKa) 9.079
Basicity (pKb) 4.918
Pharmacology
ATC code V03AC01
  • Intramuscular
  • Intraperitoneal
  • Intravenous
  • Oral
  • Subcutaneous
Pharmacokinetics:
6 hours
Related compounds
Related alkanamides
 Stearamidopropyl dimethylamine
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Deferoxamine (also known as desferrioxamine B, desferoxamine B, DFO-B, DFOA, DFB or desferal) is a bacterial siderophore produced by the Actinobacteria Streptomyces pilosus. It has medical applications as a chelating agent used to remove excess iron from the body.[1] The mesylate salt of DFO-B is commercially available.

It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[2]

Medical uses

Deferoxamine is used to treat acute iron poisoning, especially in small children. This agent is also frequently used to treat hemochromatosis, a disease of iron accumulation that can be either genetic or acquired. Acquired hemochromatosis is common in patients with certain types of chronic anemia (e.g. thalassemia and myelodysplastic syndrome) who require many blood transfusions, which can greatly increase the amount of iron in the body. Administration for chronic conditions is generally accomplished by subcutaneous injection over a period of 8–12 hours each day. Administration of deferoxamine after acute intoxication may color the urine a pinkish red, a phenomenon termed "vin rosé urine".

Apart from iron toxicity, deferoxamine can be used to treat aluminium toxicity (an excess of aluminium in the body) in select patients. In US, the drug is not FDA-approved for this use.

Deferoxamine is also used to minimize doxorubicin's cardiotoxic side effects and in the treatment of a patient with aceruloplasminemia.[3]

Mechanism

Deferoxamine acts by binding free iron in the bloodstream and enhancing its elimination in the urine. By removing excess iron, the agent reduces the damage done to various organs and tissues, such as the liver. Also, it speeds healing of nerve damage (and minimizes the extent of recent nerve trauma). Deferoxamine may modulate expression[4] and release of inflammatory mediators by specific cell types.[5]

Research

Deferoxamine is being studied as a treatment for spinal cord injury[6] and intracerebral hemorrhage.[7]

See also

References

  1. ↑ Miller, Marvin J. (1989-11-01). "Syntheses and therapeutic potential of hydroxamic acid based siderophores and analogs". Chemical Reviews 89 (7): 1563–1579. doi:10.1021/cr00097a011.
  2. ↑ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
  3. ↑ Miyajima, H.; Takahashi, Y.; Kamata, T.; Shimizu, H.; Sakai, N.; Gitlin, J. D.: Use of desferrioxamine in the treatment of aceruloplasminemia. Ann. Neurol. 41: 404-407, 1997. PMID 9066364
  4. ↑ Lee HJ, Lee J, Lee SK, Lee SK, Kim EC. Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes. BMC Cancer. 2007 Sep 13;7:176. PMID 17850672
  5. ↑ Choi EY, Kim EC, Oh HM, Kim S, Lee HJ, Cho EY, Yoon KH, Kim EA, Han WC, Choi SC, Hwang JY, Park C, Oh BS, Kim Y, Kimm KC, Park KI, Chung HT, Jun CD. Iron chelator triggers inflammatory signals in human intestinal epithelial cells: involvement of p38 and extracellular signal-regulated kinase signaling pathways. J Immunol. 2004 Jun 1;172(11):7069-77. PMID 15153529
  6. ↑ http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2009/11/human_orphan_000120.jsp&mid=WC0b01ac058001d12b
  7. ↑ Wu H, Wu T, Xu X, Wang J, Wang J. (May 2011). "Iron toxicity in mice with collagenase-induced intracerebral hemorrhage". J Cereb Blood Flow Metab. 31 (5): 1243–50. doi:10.1038/jcbfm.2010.209. PMC 3099628. PMID 21102602.
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