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Succimer

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(Redirected from Dimercaptosuccinic acid)

"Chemet" redirects here. For the violinist, see Renée Chemet.
Succimer
Clinical data
Pronunciation/ˈsʌksɪmər/
Trade namesChemet, others
Other namesDimercaptosuccinic acid
DMSA
(2R,3S)-2,3-Dimercaptosuccinic acid
meso-2,3-Dimercaptosuccinic acid
APRD01236
AHFS/Drugs.comMonograph
License data
ATC code
Legal status
Legal status
Identifiers
  • (2R,3S)-2,3-disulfanylbutanedioic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.005.597 Edit this at Wikidata
Chemical and physical data
FormulaC4H6O4S2
Molar mass182.21 g·mol−1
3D model (JSmol)
Melting point125 °C (257 °F)
  • O=C(O)[C@@H](S)[C@@H](S)C(=O)O
  • InChI=1S/C4H6O4S2/c5-3(6)1(9)2(10)4(7)8/h1-2,9-10H,(H,5,6)(H,7,8)/t1-,2+ ☒N
  • Key:ACTRVOBWPAIOHC-XIXRPRMCSA-N

Succimer, sold under the brand name Chemet among others, is a medication used to treat lead, mercury, and arsenic poisoning.[4] When radiolabeled with technetium-99m, it is used in many types of diagnostic testing.[5] A full course of Succimer lasts for 19 days of oral administration.[4] A second course should be given when more than two weeks pass after the first course.[4]

Common side effects include vomiting, diarrhea, rash, and low blood neutrophil levels.[4] Liver problems and allergic reactions may also occur with use.[4] Whether use during pregnancy is safe for the baby is unclear.[6] Dimercaptosuccinic acid is in the chelating agent family of medications.[4] It works by binding with lead and a number of other heavy metals, allowing them to leave the body in the urine.[4]

Succimer has been used medically since the 1950s.[7][8] It is on the World Health Organization's List of Essential Medicines.[9] In the United States, no generic version was available as of 2015.[10]

Medical uses

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See also: DMSA scan

Succimer is indicated for the treatment of lead poisoning in children with blood level measured above 45 μg/dL. The use of dimercaptosuccinic acid is not approved for prevention of lead poisoning in anticipation of exposure in known lead-contaminated environments. Dimercaptosuccinic acid can cross the blood–brain barrier of mice,[11] but it is not known if this is also the case in humans.[12] Even if dimercaptosuccinic acid cannot reverse the damages done to the central nervous system, it might prevent further deterioration.[13]

Succimer facilitates urinary excretion of lead, and with sufficiently aggressive treatment, can reduce lead content in the brain.[14] It also increases urinary excretion of copper and zinc.[15] Dimercaptosuccinic acid improved cognitive function in rats that had been exposed to lead, but reduced cognitive function in rats that had not been exposed to lead.[14]

Chemistry

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Succimer is an isomer of 2,3-dimercaptosuccinic acid. 2,3-dimercaptosuccinic acid is the organosulfur compound with the formula HO2CCH(SH)CH(SH)CO2H. This colorless solid contains two carboxylic acid and two thiol groups, the latter being responsible for its mildly unpleasant odour. It occurs in two diastereomers, meso and the chiral dl forms.

The 2,3-dimercaptosuccinic acid molecule has two stereocentres (two asymmetric carbon atoms), and can exist as three different stereoisomers. The 2S,3S and 2R,3R isomers are a pair of enantiomers, whereas the 2R,3S isomer (succimer) is a meso compound and thus optically inactive.

(2R,3R)-2,3-dimercaptosuccinic acid (2R,3S)-2,3-dimercaptosuccinic acid
(meso-2,3-dimercaptosuccinic acid)		 (2S,3S)-2,3-dimercaptosuccinic acid

Preparation and reactivity

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Dimercaptosuccinic acid[clarification needed] may be prepared by reacting acetylenedicarboxylic acid with sodium thiosulfate[16] or thioacetic acid followed by hydrolysis. The dimethyl ester is also known.[17]

Meso 2,3-dimercaptosuccinic acid binds to "soft" heavy metals such as Hg2+ and Pb2+, mobilizing these ions for excretion. It binds to metal cations through the thiol groups, which ionize upon complexation.

History

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Dimercaptosuccinic acid was first synthesized by V. L. Nirenburg in the Urals Polytechnic Institute, commissioned by one of the electrical enterprises of Sverdlovsk, Russia, which consumed many tons of mercury and was looking for a medicine to prevent poisoning of personnel. In 1957, Chinese scientists found that dimercaptosuccinic acid can effectively treat antimony poisoning due to overdose of tartar emetic.[18] Pronounced protective effect in animal poisoning with arsenic and mercury was first shown by I. E. Okonishnikova in 1962. In 1984, the now-defunct Bock Pharmaceutical Company requested the FDA grant approval for orphan drug status under the brand name Chemet and the FDA approved of this in 1991, providing exclusivity until 1998 which was conveyed to the successor Sanofi in 1996.[19][20]

References

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  1. ^ "Chemet- succimer capsule". DailyMed. U.S. National Library of Medicine. 12 December 2019. Retrieved 19 June 2022.
  2. ^ "Nephroscan- succimer injection, powder, lyophilized, for solution". DailyMed. U.S. National Library of Medicine. 1 March 2022. Retrieved 19 June 2022.
  3. ^ "Rotop - DMSA- kit for the preparation of technetium tc99m succimer injection injection, powder, lyophilized, for solution". DailyMed. U.S. National Library of Medicine. 9 March 2021. Retrieved 19 June 2022.
  4. ^ a b c d e f g "Succimer". The American Society of Health-System Pharmacists. Archived from the original on 16 January 2017. Retrieved 8 January 2017.
  5. ^ Biersack HJ, Grünwald F (2005). Thyroid Cancer. Springer Science & Business Media. p. 213. ISBN 9783540278450. Archived from the original on 2017-01-13.
  6. ^ "Succimer (Chemet) Use During Pregnancy". www.drugs.com. Archived from the original on 16 January 2017. Retrieved 12 January 2017.
  7. ^ Miller AL (June 1998). "Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity". Alternative Medicine Review. 3 (3): 199–207. PMID 9630737.
  8. ^ Chappell WR, Abernathy CO, Calderon RL (1999). Arsenic Exposure and Health Effects III. Elsevier. p. 350. ISBN 9780080527574. Archived from the original on 2017-01-13.
  9. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  10. ^ Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 472. ISBN 9781284057560.
  11. ^ Aaseth J, Jacobsen D, Andersen O, Wickstrøm E (March 1995). "Treatment of mercury and lead poisonings with dimercaptosuccinic acid and sodium dimercaptopropanesulfonate. A review". The Analyst. 120 (3): 853–854. Bibcode:1995Ana...120..853A. doi:10.1039/an9952000853. PMID 7741240.
  12. ^ Guzzi G, La Porta CA (February 2008). "Molecular mechanisms triggered by mercury". Toxicology. 244 (1): 1–12. Bibcode:2008Toxgy.244....1G. doi:10.1016/j.tox.2007.11.002. PMID 18077077.
  13. ^ Clarkson TW, Magos L, Myers GJ (October 2003). "The toxicology of mercury--current exposures and clinical manifestations". The New England Journal of Medicine. 349 (18): 1731–1737. doi:10.1056/nejmra022471. PMID 14585942.
  14. ^ a b Smith D, Strupp BJ (December 2013). "The scientific basis for chelation: animal studies and lead chelation". Journal of Medical Toxicology. 9 (4): 326–338. doi:10.1007/s13181-013-0339-2. PMC 3846979. PMID 24113857.
  15. ^ Bradberry S, Sheehan T, Vale A (October 2009). "Use of oral dimercaptosuccinic acid (succimer) in adult patients with inorganic lead poisoning". QJM. 102 (10): 721–732. doi:10.1093/qjmed/hcp114. PMID 19700440.
  16. ^ US 4550193, Lindemann MK, Lukenbach ER, "Process for the preparation of 2,3-dimercaptosuccinic acid and its lower alkyl esters", issued 29 October 1985, assigned to Johnson & Johnson Baby Products 
  17. ^ Gerecke M, Friedheim EA, Brossi A (1961). "Zur Kenntnis der 2,3-Dimercapto-bernsteinsäuren". Helvetica Chimica Acta. 44 (4): 955–960. doi:10.1002/hlca.19610440410.
  18. ^ Liang Y, Chu C, Tsen Y, Ting K (1957). "Studies on antibilharzial drugs. Vl. The antidotal effects of sodium dimercaptosuccinate and BAL-glucoside against tartar emetic". Acta Physiol. Sin. 21: 24–32.
  19. ^ "Search Orphan Drug Designations and Approvals". Searchable database for Orphan Designated and or Approved Products. FDA. 2013. Archived from the original on 6 November 2014. Retrieved 5 November 2014.
  20. ^ "Sanofi Buying An American Drug Concern". The New York Times. July 17, 1996. Archived from the original on 6 November 2014. Retrieved 5 November 2014.

Further reading

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  • Aposhian HV, Aposhian MM (1990). "meso-2,3-Dimercaptosuccinic acid: chemical, pharmacological and toxicological properties of an orally effective metal chelating agent". Annual Review of Pharmacology and Toxicology. 30 (1): 279–306. doi:10.1146/annurev.pa.30.040190.001431. PMID 2160791.
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