Chemistry:Cysteamine

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Short description: Chemical compound
Cysteamine
INN: mercaptamine
Cysteamine-2D-skeletal.png
Cysteamine 3D ball.png
Skeletal formula (top)
Ball-and-stick model of the cysteamine
Clinical data
Trade namesCystagon, Procysbi, Cystaran, others
Other names2-Aminoethanethiol, β-Mercaptoethylamine, 2-Mercaptoethylamine, decarboxycysteine, thioethanolamine, mercaptamine bitartrate, cysteamine (USAN US)
AHFS/Drugs.comMicromedex Detailed Consumer Information
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth, eye drops
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
Chemical and physical data
FormulaC2H7NS
Molar mass77.15 g·mol−1
3D model (JSmol)
Melting point95 to 97 °C (203 to 207 °F)

Cysteamine is a chemical compound that can be biosynthesized in mammals, including humans, by the degradation of coenzyme A. The intermediate pantetheine is broken down into cysteamine and pantothenic acid.[11] It is the biosynthetic precursor to the neurotransmitter hypotaurine.[12][11]

It is a stable aminothiol, i.e., an organic compound containing both an amine and a thiol functional groups. Cysteamine is a white, water-soluble solid. It is often used as salts of the ammonium derivative [HSCH2CH2NH3]+[13] including the hydrochloride, phosphocysteamine, and the bitartrate.[11]

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.[14][5][6][7] It removes the excessive cystine that builds up in cells of people with the disease.[11] It is available by mouth (capsule and extended release capsule) and in eye drops.[15][7][8][5][9][6][10][16]

When applied topically it can scavenge free radicals[17] and lighten skin that's been darkened as a result of post-inflammatory hyperpigmentation, sun exposure and Melasma.[18][19][20][21] Tentative evidence suggests that it may be a more effective depigmentation agent than hydroquinone, retinoids and topical corticosteroids in individuals with chronic skin discoloration.[22][23][24] 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.[25]

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.[24][25]

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.[7]

Additional adverse effects of oral cysteamine include bad breath, skin odor, vomiting, nausea, stomach pain, diarrhea, and loss of appetite.[7]

The drug is in pregnancy category C; 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.[5][6]

For eye drops, the most common adverse effects are sensitivity to light, redness, and eye pain, headache, and visual field defects.[6]

Interactions

There are no drug interactions for normal capsules or eye drops,[5][6] 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.[7] It doesn't inhibit any cytochrome P450 enzymes.[7]

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.[15] Cysteamine enters lysosomes and converts cystine into cysteine and cysteine-cysteamine mixed disulfide, both of which can exit the lysosome.[7]

Biological function

Cysteamine also promotes the transport of L-cysteine into cells, that can be further used to synthesize glutathione, which is one of the most potent intracellular antioxidants.[11]

History

First evidence regarding the therapeutic effect of cysteamine on cystinosis dates back to 1950s. Cysteamine was first approved as a drug for cystinosis in the US in 1994.[7] An extended release form was approved in 2013.[26]

Society and culture

It is approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).[15][7][8][9][10][27][28]

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.[26]

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.[11]

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.[11]

Clinical trials in Huntington's disease were begun in the 1990s and were ongoing as of 2015.[11][29]


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

References

  1. ↑ "CYSTADROPS : Cysteamine Ophthalmic Solution". https://pdf.hres.ca/dpd_pm/00049612.PDF. 
  2. ↑ "Cystagon 150 mg hard capsules - Summary of Product Characteristics (SmPC)". 19 June 2019. https://www.medicines.org.uk/emc/product/6237/smpc. 
  3. ↑ "Cystadrops 3.8 mg/mL eye drops solution - Summary of Product Characteristics (SmPC)". 19 June 2019. https://www.medicines.org.uk/emc/product/8505/smpc. 
  4. ↑ "Procysbi 25 mg gastro-resistant hard capsules - Summary of Product Characteristics (SmPC)". 17 September 2019. https://www.medicines.org.uk/emc/product/2079/smpc. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 "Cystagon- cysteamine bitartrate capsule". 29 January 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f495b76d-96c6-48e5-8fa3-30a4336628eb. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 "Cystaran- cysteamine hydrochloride solution". 22 November 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b98ee838-ed23-42a9-93b5-72579e490fba. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 7.9 "Procysbi- cysteamine bitartrate capsule, delayed release pellets Procysbi- cysteamine bitartrate granule, delayed release". DailyMed. U.S. National Library of Medicine. 23 March 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d3a3ec28-f746-463a-bb92-3bc8826db09e. 
  8. ↑ 8.0 8.1 8.2 "Procysbi EPAR". https://www.ema.europa.eu/en/medicines/human/EPAR/procysbi. 
  9. ↑ 9.0 9.1 9.2 "Cystagon EPAR". https://www.ema.europa.eu/en/medicines/human/EPAR/cystagon. 
  10. ↑ 10.0 10.1 10.2 "Cystadrops EPAR". https://www.ema.europa.eu/en/medicines/human/EPAR/cystadrops. 
  11. ↑ 11.0 11.1 11.2 11.3 11.4 11.5 11.6 11.7 "Cysteamine: an old drug with new potential". Drug Discovery Today 18 (15–16): 785–792. August 2013. doi:10.1016/j.drudis.2013.02.003. PMID 23416144. 
  12. ↑ "Oxidative Metabolism of Cysteine and Cystine". Metabolic pathways: Metabolism of sulfur compounds. 7 (3rd ed.). New York: Academic Press. 1975. p. 545. ISBN 9780323162081. https://books.google.com/books?id=2h-CyZzkPAwC&pg=PA545. Retrieved 11 January 2017. 
  13. ↑ Organic Chemistry of Bivalent Sulfur. 1. New York: Chemical Publishing Company, Inc.. 1958. pp. 398–399. 
  14. ↑ "Cystinosis". The New England Journal of Medicine 347 (2): 111–121. July 2002. doi:10.1056/NEJMra020552. PMID 12110740. 
  15. ↑ 15.0 15.1 15.2 "Cystinosis". GeneReviews. Seattle WA: University of Washington. October 6, 2016. https://www.ncbi.nlm.nih.gov/books/NBK1400/. Retrieved 11 January 2017. 
  16. ↑ "Treatment of corneal cystine crystal accumulation in patients with cystinosis". Clinical Ophthalmology 8: 2077–2084. 10 October 2014. doi:10.2147/OPTH.S36626. PMID 25336909. 
  17. ↑ "Cysteamine Cream for clearing your hyperpigmentary complexion". https://cosmeticsbusiness.com/news/article_page/Cysteamine_Cream_for_clearing_your_hyperpigmentary_complexion/127651. 
  18. ↑ "Cysteamine cream as a new skin depigmenting product". Journal of the American Academy of Dermatology 68 (4): AB189. April 2013. doi:10.1016/j.jaad.2012.12.781. https://www.jaad.org/article/S0190-9622(12)02060-9/fulltext. Retrieved 2021-10-10. 
  19. ↑ "Cysteamine cream". DermNet NZ. https://dermnetnz.org/topics/cysteamine-cream/. 
  20. ↑ "New oral and topical approaches for the treatment of melasma". International Journal of Women's Dermatology 5 (1): 30–36. February 2019. doi:10.1016/j.ijwd.2018.09.004. PMID 30809577. 
  21. ↑ "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. doi:10.1111/bjd.13424. PMID 25251767. 
  22. ↑ "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. doi:10.1111/jocd.13755. PMID 32997864. 
  23. ↑ "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. doi:10.1111/jocd.12837. PMID 30537063. 
  24. ↑ 24.0 24.1 "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. doi:10.1111/srt.12901. PMID 32585079. 
  25. ↑ 25.0 25.1 "Cysteamine cream, tranexamic acid mesotherapy reveal similar efficacy, different safety". 14 October 2020. https://www.dermatologytimes.com/view/cysteamine-cream-tranexamic-acid-mesotherapy-reveal-similar-efficacy-different-safety. 
  26. ↑ 26.0 26.1 "F.D.A. Approves Raptor Drug for Form of Cystinosis". The New York Times. 30 April 2013. https://www.nytimes.com/2013/05/01/business/fda-approves-raptor-drug-for-form-of-cystinosis.html. 
  27. ↑ "Drug Approval Package: Cystaran (cysteamine) NDA #200740". 26 August 2013. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/200740_cystaran_toc.cfm. 
  28. ↑ "Drug Approval Package: PROCYSBI (cysteamine bitartrate) Delayed-Release Capsules NDA #203389". 24 December 1999. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000TOC.cfm. 
  29. ↑ "Therapeutic advances in Huntington's Disease". Movement Disorders 30 (11): 1539–1546. September 2015. doi:10.1002/mds.26331. PMID 26226924. 
  30. ↑ "Review article: the management of paediatric nonalcoholic fatty liver disease". Alimentary Pharmacology & Therapeutics 40 (10): 1155–1170. November 2014. doi:10.1111/apt.12972. PMID 25267322. 

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