Penicillamine

Penicillamine
Systematic (IUPAC) name
(2S)-2-amino-3-methyl-3-sulfanyl-butanoic acid
Clinical data
Trade names Cuprimine
AHFS/Drugs.com monograph
  • AU: D
  • US: D (Evidence of risk)
  • ℞ (Prescription only)
Oral
Pharmacokinetic data
Bioavailability Variable
Metabolism Hepatic
Half-life 1 hour
Excretion Renal
Identifiers
52-67-5 Yes
M01CC01
PubChem CID 5852
DrugBank DB00859 Yes
ChemSpider 5643 Yes
UNII GNN1DV99GX Yes
KEGG D00496 Yes
ChEBI CHEBI:7959 Yes
ChEMBL CHEMBL1430 Yes
Chemical data
Formula C5H11NO2S
149.212 g/mol
 Yes (what is this?)  (verify)

Penicillamine is a pharmaceutical of the chelator class.[1] It have been sold under the trade names of Cuprimine and Depen. The pharmaceutical form is D-penicillamine, as L-penicillamine is toxic (it inhibits the action of pyridoxine).[2] It is an α-amino acid metabolite of penicillin, although it has no antibiotic properties.[3]

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[4]

Medical uses

Penicillamine is used as a form of immunosuppression to treat rheumatoid arthritis. It works by reducing numbers of T-lymphocytes, inhibiting macrophage function, decreasing IL-1, decreasing rheumatoid factor, and preventing collagen from cross-linking.[5]

It is used as a chelating agent:

Adverse effects

Bone marrow suppression, dysgeusia, anorexia, vomiting and diarrhea are the most common side effects, occurring in ~20-30% of the patients treated with penicillamine.[5][10]

Other possible adverse effects include:

Besides, people allergic to penicillin may have hypersensitivity to penicillamine.[3]

History

John Walshe first described the use of penicillamine in Wilson's disease in 1956.[17] He had discovered the compound in the urine of patients (including himself) who had taken penicillin, and experimentally confirmed that it increased urinary copper excretion by chelation. He had initial difficulty convincing several world experts of the time (Denny Brown and Cumings) of its efficacy, as they held that Wilson's disease was not primarily a problem of copper homeostasis but of amino acid metabolism, and that dimercaprol should be used as a chelator. Later studies confirmed both the copper-centered theory and the efficacy of D-penicillamine. Walshe also pioneered other chelators in Wilson's such as triethylene tetramine, 2HCl, and tetrathiomolybdate.[18]

Penicillamine has been used in rheumatoid arthritis since the first successful case in 1964.[19] Cuprimine went out of production in 2003.

References

  1. ↑ 1.0 1.1 Peisach, J.; Blumberg, W. E. (1969). "A mechanism for the action of penicillamine in the treatment of Wilson's disease". Molecular pharmacology 5 (2): 200–209. PMID 4306792.
  2. ↑ Jaffe, I. A.; Altman, K.; Merryman, P. (1964). "The Antipyridoxine Effect of Penicillamine in Man*". Journal of Clinical Investigation 43 (10): 1869–1873. doi:10.1172/JCI105060. PMC 289631. PMID 14236210.
  3. ↑ 3.0 3.1 Parker, C. W.; Shapiro, J.; Kern, M.; Eisen, H. N. (1962). "Hypersensitivity to penicillenic acid derivatives in human beings with penicillin allergy". The Journal of experimental medicine 115 (4): 821–838. doi:10.1084/jem.115.4.821. PMC 2137514. PMID 14483916.
  4. ↑ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.
  5. ↑ 5.0 5.1 5.2 5.3 Camp, A. V. (1977). "Penicillamine in the treatment of rheumatoid arthritis". Proceedings of the Royal Society of Medicine 70 (2): 67–69. PMC 1542978. PMID 859814.
  6. ↑ 6.0 6.1 Rosenberg, L. E.; Hayslett, J. P. (1967). "Nephrotoxic Effects of Penicillamine in Cystinuria". JAMA: the Journal of the American Medical Association 201 (9): 698. doi:10.1001/jama.1967.03130090062021.
  7. ↑ Steen, V. D.; Medsger Jr, T. A.; Rodnan, G. P. (1982). "D-Penicillamine therapy in progressive systemic sclerosis (scleroderma): A retrospective analysis". Annals of internal medicine 97 (5): 652–659. doi:10.7326/0003-4819-97-5-652. PMID 7137731.
  8. ↑ Peterson, R. G.; Rumack, B. H. (1977). "D-Penicillamine therapy of acute arsenic poisoning". The Journal of Pediatrics 91 (4): 661–666. doi:10.1016/S0022-3476(77)80528-3. PMID 908992.
  9. ↑ Hall, A. H. (2002). "Chronic arsenic poisoning". Toxicology Letters 128 (1–3): 69–72. doi:10.1016/S0378-4274(01)00534-3. PMID 11869818.
  10. ↑ Grasedyck, K. (1988). "D-penicillamine--side effects, pathogenesis and decreasing the risks". Zeitschrift fur Rheumatologie. 47 Suppl 1: 17–19. PMID 3063003.
  11. ↑ 11.0 11.1 Fishel, B.; Tishler, M.; Caspi, D.; Yaron, M. (1989). "Fatal aplastic anaemia and liver toxicity caused by D-penicillamine treatment of rheumatoid arthritis". Annals of the rheumatic diseases 48 (7): 609–610. doi:10.1136/ard.48.7.609. PMC 1003826. PMID 2774703.
  12. ↑ Table 14-2 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
  13. ↑ Chalmers, A.; Thompson, D.; Stein, H. E.; Reid, G.; Patterson, A. C. (1982). "Systemic lupus erythematosus during penicillamine therapy for rheumatoid arthritis". Annals of internal medicine 97 (5): 659–663. doi:10.7326/0003-4819-97-5-659. PMID 6958210.
  14. ↑ Bolognia, Jean; et al. (2007). Dermatology. Philadelphia: Elsevier. ISBN 1-4160-2999-0. 2nd edition.
  15. ↑ Underwood, J. C. E. (2009). General and systemic Pathology. Elsevier Limited. ISBN 978-0-443-06889-8.
  16. ↑ Taylor, Cumming, Corenblum (January 31, 1981). "Successful treatment of D-penicillamine-induced breast gigantism with danazol". Taylor, Cumming, Corenblum. Br Med J. Retrieved 2013-04-06.
  17. ↑ Walshe JM (January 1956). "Wilson's disease; new oral therapy". Lancet 267 (6906): 25–6. doi:10.1016/S0140-6736(56)91859-1. PMID 13279157.
  18. ↑ Walshe JM (August 2003). "The story of penicillamine: a difficult birth". Mov. Disord. 18 (8): 853–9. doi:10.1002/mds.10458. PMID 12889074.
  19. ↑ Jaffe, I. A. (1964). "Rheumatoid Arthritis with Arteritis; Report of a Case Treated with Penicillamine". Annals of internal medicine 61: 556–563. doi:10.7326/0003-4819-61-3-556. PMID 14218939.

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