title: Chelation in metal intoxication--Principles and paradigms.
abstract: The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The clinical use of the old chelators EDTA (ethylenediamine tetraacetate) and BAL (2,3-dimercaptopropanol) is now limited due to the inconvenience of parenteral administration, their own toxicity and tendency to increase the neurotoxicity of several metals. The hydrophilic dithiol chelators DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercapto-propanesulphonate) are less toxic and more efficient than BAL in the clinical treatment of heavy metal poisoning, and available as capsules for oral use. In copper overload, DMSA appears to be a potent antidote, although d-penicillamine is still widely used. In the chelation of iron, the thiols are inefficient, since iron has higher affinity for ligands with nitrogen and oxygen, but the new oral iron antidotes deferiprone and desferasirox have entered into the clinical arena. Comparisons of these agents and deferoxamine infusions are in progress. General principles for research and development of new chelators are briefly outlined in this review.
authors.affiliation: Innlandet Hospital Trust, Kongsvinger Hospital Division, Kongsvinger, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Aaseth
authors.affiliation: Faculty of Public Health, Hedmark University College, 2418 Elverum, Norway. Electronic address: marit.skaug@hihm.no.
authors.forename: Marit Aralt
authors.initials: MA
authors.lastname: Skaug
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Science, Systems and Models, Roskilde University, Roskilde, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Andersen
mesh_terms: D000284:Administration, Oral; D000931:Antidotes / Q000494:pharmacology / Q000627:therapeutic use; D001565:Benzoates / Q000494:pharmacology; D002614:Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077588:Deferasirox; D000077543:Deferiprone; D003676:Deferoxamine / Q000009:adverse effects / Q000627:therapeutic use; D000075322:Heavy Metal Poisoning; D006801:Humans; D010396:Penicillamine / Q000627:therapeutic use; D011041:Poisoning / Q000188:drug therapy*; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use; D004113:Succimer / Q000009:adverse effects / Q000627:therapeutic use; D014230:Triazoles / Q000494:pharmacology; D014266:Trientine / Q000627:therapeutic use; D014494:Unithiol / Q000627:therapeutic use
chemical_list: D000931:Antidotes; D001565:Benzoates; D002614:Chelating Agents; D011728:Pyridones; D014230:Triazoles; D000077543:Deferiprone; D014494:Unithiol; D004113:Succimer; D010396:Penicillamine; D003676:Deferoxamine; D014266:Trientine; D000077588:Deferasirox
keywords: DMPS; DMSA; Deferasirox; Deferiprone; Deferoxamine