Cysteamine Explained

Inn:mercaptamine
Iupac Name:2-Aminoethane-1-thiol
Inn Ema:mercaptamine
Usan:cysteamine
Tradename:Cystagon, Procysbi, Cystaran, others
Dailymedid:Cysteamine
Pregnancy Au:B3
Routes Of Administration:By mouth, eye drops
Atc Prefix:A16
Atc Suffix:AA04
Legal Ca:Rx-only
Legal Ca Comment:[1] [2]
Legal Uk:POM
Legal Uk Comment:[3] [4] [5]
Legal Us:Rx-only
Legal Eu:Rx-only
Legal Status:Rx-only
Index2 Label:as salt
Cas Number:60-23-1
Pubchem:6058
Iuphar Ligand:7440
Drugbank:DB00847
Chemspiderid:5834
Unii:5UX2SD1KE2
Kegg:D03634
Kegg2:D10468
Chebi:17141
Chembl:602
Pdb Ligand:DHL
Synonyms:2-Aminoethanethiol, β-Mercaptoethylamine, 2-Mercaptoethylamine, decarboxycysteine, thioethanolamine, mercaptamine bitartrate
C:2
H:7
N:1
S:1
Smiles:C(CS)N
Stdinchi:1S/C2H7NS/c3-1-2-4/h4H,1-3H2
Stdinchikey:UFULAYFCSOUIOV-UHFFFAOYSA-N
Melting Point:95 to 97

Cysteamine is an organosulfur compound with the formula . A white, water-soluble solid, it contains both an amine and a thiol functional groups. It is often used as salts of the ammonium derivative [HSCH<sub>2</sub>CH<sub>2</sub>NH<sub>3</sub>]+[6] including the hydrochloride, phosphocysteamine, and the bitartrate.The intermediate pantetheine is broken down into cysteamine and pantothenic acid.[7]

It is biosynthesized in mammals, including humans, by the degradation of coenzyme A. It is the biosynthetic precursor to the neurotransmitter hypotaurine.[8] [7]

Medical uses

As a medication, cysteamine, sold under the brand name Cystagon among others, is indicated to treat cystinosis, a lysosomal storage disease characterized by the abnormal accumulation of cystine, the oxidized dimer of the amino acid cysteine.[9] It removes the excessive cystine that builds up in cells of people with the disease.[7] It is available by mouth (capsule and extended release capsule) and in eye drops.[10] [11] [12] [13] [14] [15] [16]

When applied topically it can lighten skin that's been darkened as a result of post-inflammatory hyperpigmentation, sun exposure and Melasma.[17] [18] [19] [20] Tentative evidence suggests that it may be a more effective depigmentation agent than hydroquinone, retinoids and topical corticosteroids in individuals with chronic skin discoloration.[21] [22] [23] Topical application of cysteamine cream has also demonstrated similar efficacy to intradermal tranexamic acid injections for the treatment of Melasma but with much fewer adverse effects.[24]

Adverse effects

Topical use

The most important adverse effect related to topical use might be skin irritation. However it's significantly better tolerated than alternative skin lightening treatments with similar efficacy.

Oral use

The label for oral formulations of cysteamine carry warnings about symptoms similar to Ehlers-Danlos syndrome, severe skin rashes, ulcers or bleeding in the stomach and intestines, central nervous symptoms including seizures, lethargy, somnolence, depression, and encephalopathy, low white blood cell levels, elevated alkaline phosphatase, and idiopathic intracranial hypertension that can cause headache, tinnitus, dizziness, nausea, double or blurry vision, loss of vision, and pain behind the eye or pain with eye movement.

Additional adverse effects of oral cysteamine include bad breath, skin odor, vomiting, nausea, stomach pain, diarrhea, and loss of appetite.

The risks of cysteamine to a fetus are not known but it harms babies in animal models at doses less than those given to people.

For eye drops, the most common adverse effects are sensitivity to light, redness, and eye pain, headache, and visual field defects.[14]

Interactions

There are no drug interactions for normal capsules or eye drops,[12] [14] but the extended release capsules should not be taken with drugs that affect stomach acid like proton pump inhibitors or with alcohol, as they can cause the drug to be released too quickly.[10] It doesn't inhibit any cytochrome P450 enzymes.[10]

Pharmacology

People with cystinosis lack a functioning transporter (cystinosin) which transports cystine from the lysosome to the cytosol. This ultimately leads to buildup of cystine in lysosomes, where it crystallizes and damages cells.[25] Cysteamine enters lysosomes and converts cystine into cysteine and cysteine-cysteamine mixed disulfide, both of which can exit the lysosome.[10]

Cysteamine also promotes the transport of L-cysteine into cells.[7]

Society and culture

It is approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).[25] [10] [26] [27]

In 2013, the regular capsule of cysteamine cost about $8,000 per year; the extended release form that was introduced that year was priced at $250,000 per year.

History

The therapeutic effect of cysteamine on cystinosis was reported in the 1950s. Cysteamine was approved as a drug for cystinosis in the US in 1994.[10] An extended release form was approved in 2013.[28]

Research

It was studied in in vitro and animal models for radiation protection in the 1950s, and in similar models from the 1970s onwards for sickle cell anemia, effects on growth, its ability to modulate the immune system, and as a possible inhibitor of HIV.[7]

In the 1970s it was tested in clinical trials for Paracetamol toxicity which it failed, and in clinical trials for systemic lupus erythematosus in the 1990s and early 2000s, which it also failed.

Clinical trials in Huntington's disease were begun in the 1990s and were ongoing as of 2015.[7] [29]

, it was in clinical trials for Parkinson's disease, malaria, radiation sickness, neurodegenerative disorders, neuropsychiatric disorders, and cancer treatment.[7]

It has been studied in clinical trials for pediatric nonalcoholic fatty liver disease.[30]

Notes and References

  1. Web site: CYSTADROPS : Cysteamine Ophthalmic Solution. Pdf.hres.ca. 8 June 2022. 10 June 2022. https://web.archive.org/web/20220610034106/https://pdf.hres.ca/dpd_pm/00049612.PDF. live.
  2. Web site: Genetic disorders . . 9 May 2018 . 13 April 2024.
  3. Web site: Cystagon 150 mg hard capsules - Summary of Product Characteristics (SmPC) . Medicines.org.uk . 19 June 2019 . 28 April 2020 . 9 June 2021 . https://web.archive.org/web/20210609150203/https://www.medicines.org.uk/emc/product/6237/smpc . live .
  4. Web site: Cystadrops 3.8 mg/mL eye drops solution - Summary of Product Characteristics (SmPC) . (emc) . 19 June 2019 . 9 June 2020 . 9 June 2020 . https://web.archive.org/web/20200609160936/https://www.medicines.org.uk/emc/product/8505/smpc . live .
  5. Web site: Procysbi 25 mg gastro-resistant hard capsules - Summary of Product Characteristics (SmPC) . Medicines.org.uk . 17 September 2019 . 9 June 2020 . 22 January 2021 . https://web.archive.org/web/20210122225837/https://www.medicines.org.uk/emc/product/2079/smpc . live .
  6. Book: Reid EE . Organic Chemistry of Bivalent Sulfur . 1. 1958 . Chemical Publishing Company, Inc. . New York. 398–399.
  7. Besouw M, Masereeuw R, van den Heuvel L, Levtchenko E . Cysteamine: an old drug with new potential . Drug Discovery Today . 18 . 15–16 . 785–792 . August 2013 . 23416144 . 10.1016/j.drudis.2013.02.003 .
  8. Book: Singer TP . Greenberg DM . Metabolic pathways: Metabolism of sulfur compounds . 7 . 1975 . Academic Press . New York . 9780323162081 . 3rd . https://books.google.com/books?id=2h-CyZzkPAwC&pg=PA545 . Oxidative Metabolism of Cysteine and Cystine . 545 . 11 January 2017 . 7 June 2021 . https://web.archive.org/web/20210607203433/https://books.google.com/books?id=2h-CyZzkPAwC&pg=PA545 . live .
  9. Gahl WA, Thoene JG, Schneider JA . Cystinosis . The New England Journal of Medicine . 347 . 2 . 111–121 . July 2002 . 12110740 . 10.1056/NEJMra020552 .
  10. Web site: Procysbi- cysteamine bitartrate capsule, delayed release pellets Procysbi- cysteamine bitartrate granule, delayed release . DailyMed . U.S. National Library of Medicine . 23 March 2020 . 27 April 2020 . 25 March 2021 . https://web.archive.org/web/20210325222626/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d3a3ec28-f746-463a-bb92-3bc8826db09e . live .
  11. Web site: Procysbi EPAR . European Medicines Agency (EMA) . 27 April 2020 . 4 August 2020 . https://web.archive.org/web/20200804120038/https://www.ema.europa.eu/en/medicines/human/EPAR/procysbi . live .
  12. Web site: Cystagon- cysteamine bitartrate capsule . DailyMed . 29 January 2019 . 27 April 2020 . 25 March 2021 . https://web.archive.org/web/20210325054850/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f495b76d-96c6-48e5-8fa3-30a4336628eb . live .
  13. Web site: Cystagon EPAR . European Medicines Agency (EMA) . 27 April 2020 . 11 November 2020 . https://web.archive.org/web/20201111092623/https://www.ema.europa.eu/en/medicines/human/EPAR/cystagon . live .
  14. Web site: Cystaran- cysteamine hydrochloride solution . DailyMed . 22 November 2019 . 27 April 2020 . 24 March 2021 . https://web.archive.org/web/20210324215617/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b98ee838-ed23-42a9-93b5-72579e490fba . live .
  15. Web site: Cystadrops EPAR . European Medicines Agency (EMA) . 27 April 2020 . 4 August 2020 . https://web.archive.org/web/20200804152527/https://www.ema.europa.eu/en/medicines/human/EPAR/cystadrops . live .
  16. Shams F, Livingstone I, Oladiwura D, Ramaesh K . Treatment of corneal cystine crystal accumulation in patients with cystinosis . Clinical Ophthalmology . 8 . 2077–2084 . 10 October 2014 . 25336909 . 4199850 . 10.2147/OPTH.S36626 . free .
  17. Hsu C, Mahdi H, Pourahmadi M, Ahmadi S . April 2013. Cysteamine cream as a new skin depigmenting product . Journal of the American Academy of Dermatology. 68. 4. AB189. 10.1016/j.jaad.2012.12.781. 2021-10-10 .
  18. Web site: Cysteamine cream . DermNet NZ . 2021-06-29 . 29 June 2021 . https://web.archive.org/web/20210629033843/https://dermnetnz.org/topics/cysteamine-cream/ . live .
  19. Grimes PE, Ijaz S, Nashawati R, Kwak D . New oral and topical approaches for the treatment of melasma . International Journal of Women's Dermatology . 5 . 1 . 30–36 . February 2019 . 30809577 . 6374710 . 10.1016/j.ijwd.2018.09.004 .
  20. Mansouri P, Farshi S, Hashemi Z, Kasraee B . Evaluation of the efficacy of cysteamine 5% cream in the treatment of epidermal melasma: a randomized double-blind placebo-controlled trial . The British Journal of Dermatology . 173 . 1 . 209–217 . July 2015 . 25251767 . 10.1111/bjd.13424 . 21618233 .
  21. Mathe N, Balogun M, Yoo J . A case report on the use of topical cysteamine 5% cream in the management of refractory postinflammatory hyperpigmentation (PIH) resistant to triple combination cream (hydroquinone, topical corticosteroids, and retinoids) . Journal of Cosmetic Dermatology . 20 . 1 . 204–206 . January 2021 . 32997864 . 10.1111/jocd.13755 . 222163129 .
  22. Kasraee B, Mansouri P, Farshi S . Significant therapeutic response to cysteamine cream in a melasma patient resistant to Kligman's formula . Journal of Cosmetic Dermatology . 18 . 1 . 293–295 . February 2019 . 30537063 . 10.1111/jocd.12837 . 54481706 .
  23. Karrabi M, David J, Sahebkar M . Clinical evaluation of efficacy, safety and tolerability of cysteamine 5% cream in comparison with modified Kligman's formula in subjects with epidermal melasma: A randomized, double-blind clinical trial study . Skin Research and Technology . 27 . 1 . 24–31 . January 2021 . 32585079 . 10.1111/srt.12901 . 220078010 .
  24. Web site: Hilton L. 14 October 2020. Cysteamine cream, tranexamic acid mesotherapy reveal similar efficacy, different safety. 2021-06-29. Dermatology Times. 29 June 2021. https://web.archive.org/web/20210629035428/https://www.dermatologytimes.com/view/cysteamine-cream-tranexamic-acid-mesotherapy-reveal-similar-efficacy-different-safety. live.
  25. Book: Nesterova G, Gahl WA . Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A . Cystinosis . https://www.ncbi.nlm.nih.gov/books/NBK1400/ . GeneReviews . University of Washington . Seattle WA . 20301574 . October 6, 2016 . 11 January 2017 . 5 April 2011 . https://web.archive.org/web/20110405074013/https://www.ncbi.nlm.nih.gov/books/NBK1400/ . live .
  26. Web site: Drug Approval Package: Cystaran (cysteamine) NDA #200740 . U.S. Food and Drug Administration (FDA) . 26 August 2013 . 9 June 2020 . 9 June 2020 . https://web.archive.org/web/20200609160941/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/200740_cystaran_toc.cfm . live .
  27. Web site: Drug Approval Package: PROCYSBI (cysteamine bitartrate) Delayed-Release Capsules NDA #203389 . U.S. Food and Drug Administration (FDA) . 24 December 1999 . 9 June 2020 . 9 June 2020 . https://web.archive.org/web/20200609160946/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000TOC.cfm . live .
  28. News: Pollack A . F.D.A. Approves Raptor Drug for Form of Cystinosis. The New York Times. 30 April 2013. 26 February 2017. 10 September 2021. https://web.archive.org/web/20210910154630/https://www.nytimes.com/2013/05/01/business/fda-approves-raptor-drug-for-form-of-cystinosis.html. live.
  29. Shannon KM, Fraint A . Therapeutic advances in Huntington's Disease . Movement Disorders . 30 . 11 . 1539–1546 . September 2015 . 26226924 . 10.1002/mds.26331 . 31037666 .
  30. Mitchel EB, Lavine JE . Review article: the management of paediatric nonalcoholic fatty liver disease . Alimentary Pharmacology & Therapeutics . 40 . 10 . 1155–1170 . November 2014 . 25267322 . 10.1111/apt.12972 . 21263419 . free .

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