Penicillamine

Overview

Penicillamine, sold under the brand name 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.[1][2] WP

Penicillamine was approved for medical use in the United States in 1970. It is on the World Health Organization's List of Essential Medicines.[1][3] WP

Uses, dosage and effects

Medical uses

It is used as a chelating agent: WP

• In Wilson's disease, a rare genetic disorder of copper metabolism, penicillamine treatment relies on its binding to accumulated copper and elimination through urine. Succimer (dimercaptosuccinic acid) is increasingly used in place of penicillamine.[4][5] WP
• Penicillamine was the second line treatment for arsenic poisoning, after dimercaprol (BAL). It is no longer recommended.[6][7] WP

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.[8] WP

Penicillamine has been used to treat scleroderma.[9] WP

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.[10] WP

Risks and side effects

Adverse effects

Common side effects include rash, loss of appetite, nausea, diarrhea, and low 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.[1][2] WP

Bone marrow suppression, dysgeusia, anorexia, vomiting, and diarrhea are the most common side effects, occurring in ~20–30% of the patients treated with penicillamine.[11][12] WP

Other possible adverse effects include: WP

• Nephropathy[8][11] WP
• Hepatotoxicity[13] WP
• Membranous glomerulonephritis[14] WP
• Aplastic anemia (idiosyncratic)[13] WP
• Antibody-mediated myasthenia gravis and Lambert–Eaton myasthenic syndrome, which may persist even after its withdrawal[11] WP
• Drug-induced systemic lupus erythematosus[15] WP
• Elastosis perforans serpiginosa[16] WP
• Toxic myopathies[17] WP
• Unwanted breast growth (macromastia)[18] WP
• Oligospermia WP

History

History

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 and tetrathiomolybdate.[19][20] WP

Penicillamine was first synthesized by John Cornforth under supervision of Robert Robinson.[21] WP

Penicillamine has been used in rheumatoid arthritis since the first successful case in 1964.[22] WP

Chemistry

Formula

C5H11NO2S PC

Molar mass (g/mol)

149.21 PC

IUPAC name (computed by PubChem)

(2S)-2-amino-3-methyl-3-sulfanylbutanoic acid PC

SMILES

CC(C)([C@H](C(=O)O)N)S PC

InChIKey

VVNCNSJFMMFHPL-VKHMYHEASA-N PC

PubChem CID

5852

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Penicillamine
2. Other WHO Model Formulary 2008. 2009
3. Other World Health Organization model list of essential medicines: 21st list 2019. 2019
4. Journal / agency Peisach J, Blumberg WE. A mechanism for the action of penicillamine in the treatment of Wilson's disease. Molecular Pharmacology. March 1969. doi:10.1016/S0026-895X(25)14659-2 · PMID 4306792
5. Journal / agency Aaseth J, Skaug MA, Cao Y, Andersen O. Chelation in metal intoxication--Principles and paradigms. Journal of Trace Elements in Medicine and Biology. 2015. doi:10.1016/j.jtemb.2014.10.001 · PMID 25457281
6. Journal / agency Peterson RG, Rumack BH. D-penicillamine therapy of acute arsenic poisoning. The Journal of Pediatrics. October 1977. doi:10.1016/S0022-3476(77)80528-3 · PMID 908992
7. Journal / agency Hall AH. Chronic arsenic poisoning. Toxicology Letters. March 2002. doi:10.1016/S0378-4274(01)00534-3 · PMID 11869818
8. Journal / agency Rosenberg LE, Hayslett JP. Nephrotoxic effects of penicillamine in cystinuria. JAMA. August 1967. doi:10.1001/jama.1967.03130090062021 · PMID 6071831
9. Journal / agency Steen VD, Medsger TA, Rodnan GP. D-Penicillamine therapy in progressive systemic sclerosis (scleroderma): a retrospective analysis. Annals of Internal Medicine. November 1982. doi:10.7326/0003-4819-97-5-652 · PMID 7137731
10. Other Cuprimine (penicillamine) Capsules for Oral Use. U.S. Full Prescribing Information
11. Journal / agency Camp AV. Penicillamine in the treatment of rheumatoid arthritis. Proceedings of the Royal Society of Medicine. February 1977. doi:10.1177/003591577707000201 · PMID 859814 · PMC1542978
12. Journal / agency Grasedyck K. D-penicillamine--side effects, pathogenesis and decreasing the risks. Zeitschrift für Rheumatologie. 1988. PMID 3063003
13. Journal / agency Fishel B, Tishler M, Caspi D, Yaron M. Fatal aplastic anaemia and liver toxicity caused by D-penicillamine treatment of rheumatoid arthritis. Annals of the Rheumatic Diseases. July 1989. doi:10.1136/ard.48.7.609 · PMID 2774703 · PMC1003826
14. Other Mitchell RS, Kumar V, Abbas AK, Fausto N. Robbins Basic Pathology. 2007
15. Journal / agency Chalmers A, Thompson D, Stein HE, Reid G, Patterson AC. Systemic lupus erythematosus during penicillamine therapy for rheumatoid arthritis. Annals of Internal Medicine. November 1982. doi:10.7326/0003-4819-97-5-659 · PMID 6958210
16. Other Bolognia J, Rapini RP, Jorizzo JL, Jorizzo JL, Schaffer JV. Dermatology. 2007
17. Other Underwood JC. General and Systemic Pathology. 2009
18. Journal / agency Taylor PJ, Cumming DC, Corenblum B. Successful treatment of D-penicillamine-induced breast gigantism with danazol. British Medical Journal. January 1981. doi:10.1136/bmj.282.6261.362-a · PMID 6780026 · PMC1504185
19. Journal / agency Walshe JM. Wilson's disease; new oral therapy. Lancet. January 1956. doi:10.1016/S0140-6736(56)91859-1 · PMID 13279157
20. Journal / agency Walshe JM. The story of penicillamine: a difficult birth. Movement Disorders. August 2003. doi:10.1002/mds.10458 · PMID 12889074
21. Other Oakes EH. Encyclopedia of World Scientists. 2007
22. Journal / agency Jaffe IA. Rheumatoid Arthritis with Arteritis; Report of a Case Treated with Penicillamine. Annals of Internal Medicine. September 1964. doi:10.7326/0003-4819-61-3-556 · PMID 14218939

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