Penicillamine Clinical data Trade names Cuprimine, Cuprenyl, Depen, others Other names D-penicillamine AHFS/ Drugs.com Monograph MedlinePlus a618021 License data
AU: D US: D (Evidence of risk) Routes of administration By mouth ( capsules) ATC code Legal status Legal status
US: ?-only In general (Prescription only) Pharmacokinetic data Bioavailability Variable Metabolism Liver Elimination 1 hour Excretion Kidney Identifiers
(2 S)-2-amino-3-methyl-3-sulfanylbutanoic acid CAS Number PubChem CID IUPHAR/BPS DrugBank ChemSpider UNII KEGG ChEBI ChEMBL CompTox Dashboard ( EPA) ECHA InfoCard 100.000.136 Chemical and physical data Formula C 5 H 11 N O 2 S Molar mass 149.212 g/mol g·mol -1 3D model ( JSmol)
(verify) Penicillamine, sold under the trade names of Cuprimine among others, is a medication primarily used for the treatment of Wilson's disease. It is also used for people with  kidney stones who have high urine cystine levels, rheumatoid arthritis, and various heavy metal poisonings.  It is taken by mouth.  
Common side effects include rash, loss of appetite, nausea, diarrhea, and
low blood white blood cell levels. Other serious side effects include  liver problems, obliterative bronchiolitis, and myasthenia gravis. It is not recommended in people with  lupus erythematosus. Use during  pregnancy may result in harm to the baby. Penicillamine works by  binding heavy metals; the resulting penicillamine-metal complexes are then removed from the body in the urine. 
Penicillamine was approved for medical use in the United States in 1970.
It is on the  World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. The wholesale cost in the  developing world is about US$0.55 to $1.20 a dose. A month supply in the United Kingdom costs the  NHS about £178 as of 2019. In the United States the costs of the medication increased from about 500 USD to 24,000 USD per month in 2016.  
It is used as a chelating agent:
In Wilson's disease, a rare genetic disorder of
copper metabolism, penicillamine treatment relies on its binding to accumulated copper and elimination through urine.  Penicillamine was the second line treatment for arsenic poisoning, after dimercaprol (BAL). It is no longer recommended.  
In cystinuria, a hereditary disorder in which high urine cystine levels lead to the formation of
cystine stones, penicillamine binds with cysteine to yield a mixed disulfide which is more soluble than cystine. 
Penicillamine has been used to treat
Penicillamine can be used as a
disease-modifying antirheumatic drug (DMARD) to treat severe active rheumatoid arthritis in patients who have failed to respond to an adequate trial of conventional therapy, although it is rarely used today due to availability of  TNF inhibitors and other agents, such as tocilizumab and tofacitinib. Penicillamine works by reducing numbers of T-lymphocytes, inhibiting macrophage function, decreasing IL-1, decreasing rheumatoid factor, and preventing collagen from cross-linking.
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.  
Other possible adverse effects include:
Penicillamine is a tri
functional organic compound, consisting of a thiol, an amine, and a carboxylic acid. It is structurally similar to the ?- amino acid cysteine, but with geminal dimethyl substituents ? to the thiol. Like most amino acids, it is a colorless solid that exists in the zwitterionic form at physiological pH. Of its two enantiomers, L-penicillamine (having R absolute configuration) is toxic because it inhibits the action of pyridoxine (also known as vitamin B). 6 That enantiomer is a  metabolite of penicillin but has no antibiotic properties itself. A variety of penicillamine-copper complex structures are known.  
John Walshe first described the use of penicillamine in Wilson's disease in 1956.
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 di hydrochloride and tetrathiomolybdate. 
Penicillamine was first synthesized by
John Cornforth ( Somerville College, Oxford) under supervision of Robert Robinson. 
Penicillamine has been used in rheumatoid arthritis since the first successful case in 1964.
^ a b c d e f
"Penicillamine". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016 . Retrieved 2016.
^ a b c d
World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. pp. 64, 592. hdl: 10665/44053. ISBN . 9789241547659
World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva. hdl: 10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
"Penicillamine". International Drug Price Indicator Guide . Retrieved 2016.
British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 1064. ISBN . 9780857113382
Petersen, Melody. "How 4 drug companies rapidly raised prices on life-saving drugs". Los Angeles Times . Retrieved 2019.
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.
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.
Hall, A. H. (2002). "Chronic arsenic poisoning". Toxicology Letters. 128 (1-3): 69-72. doi: 10.1016/S0378-4274(01)00534-3. PMID 11869818.
^ a b
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.
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.
"Cuprimine (penicillamine) Capsules for Oral Use. U.S. Full Prescribing Information" (PDF). Archived (PDF) from the original on 8 September 2015 . Retrieved 2016.
^ a b c
Camp, A. V. (1977). "Penicillamine in the treatment of rheumatoid arthritis". Proceedings of the Royal Society of Medicine. 70 (2): 67-69. doi: 10.1177/003591577707000201. PMC . 1542978 PMID 859814.
Grasedyck, K. (1988). " D-Penicillamine--side effects, pathogenesis and decreasing the risks". Zeitschrift für Rheumatologie. 47 Suppl 1: 17-19. PMID 3063003.
^ a b
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.
Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). "Table 14-2". Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN . 978-1-4160-2973-1
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.
Bolognia, Jean; et al. (2007). Dermatology. Philadelphia: Elsevier. ISBN . 978-1-4160-2999-1 2nd edition.
Underwood, J. C. E. (2009). General and Systemic Pathology. Elsevier Limited. ISBN . 978-0-443-06889-8
Taylor; Cumming; Corenblum (31 January 1981). "Successful treatment of . D-penicillamine-induced breast gigantism with danazol" Br Med J. 282 (6261): 362-3. doi: 10.1136/bmj.282.6261.362-a. PMC . 1504185 PMID 6780026.
Aronson, J. K. (2010). . Amsterdam: Elsevier Science. p. 613. Meyler's Side Effects of Analgesics and Anti-inflammatory Drugs ISBN . 9780080932941 Archived from the original on 10 September 2017.
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.
Birker, Paul J. M. W. L.; Freeman, Hans C. (1977). "Structure, properties, and function of a copper(I)-copper(II) complex of D-penicillamine: pentathallium(I) ? 8-chloro-dodeca( D-penicillaminato)octacuprate(I)hexacuprate(II) n-hydrate". J. Am. Chem. Soc. 99 (21): 6890-6899. doi: 10.1021/ja00463a019. PMID 903530.
Walshe, J. M. (January 1956). "Wilson's disease; new oral therapy". Lancet. 270 (6906): 25-6. doi: 10.1016/S0140-6736(56)91859-1. PMID 13279157.
Walshe, J. M. (August 2003). "The story of penicillamine: a difficult birth". Mov. Disord. 18 (8): 853-9. doi: 10.1002/mds.10458. PMID 12889074.
Oakes, Elizabeth H. (2007). . Infobase Publishing. p. 156. Encyclopedia of World Scientists ISBN . 9781438118826
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.
"Penicillamine". Drug Information Portal. U.S. National Library of Medicine.