Penicillamine

 ( Alpha-amino Acids ) 

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 cystinuria, rheumatoid arthritis, and various heavy metal poisonings. It is taken by mouth.

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

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Medical uses 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. Succimer (dimercaptosuccinic acid) is increasingly used in place of penicillamine.
• 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 scleroderma.

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 and other agents, such as tocilizumab and tofacitinib. Penicillamine works by reducing numbers of T cell, inhibiting macrophage function, decreasing IL-1, decreasing rheumatoid factor, and preventing collagen from cross-linking.

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Adverse effects Common side effects include rash, loss of appetite, nausea, diarrhea, and leukopenia. 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.

(2025). 9789241547659, World Health Organization. ISBN 9789241547659

Penicillamine works by chelating agent; the resulting penicillamine–metal complexes are then removed from the body in the urine.

Bone marrow suppression, dysgeusia, anorexia, vomiting, and diarrhea are the most common , occurring in ~20–30% of the patients treated with penicillamine.

Other possible adverse effects include:

• Nephropathy
• Hepatotoxicity
• Membranous glomerulonephritis
  (2025). 9781416029731, Saunders. ISBN 9781416029731
• Aplastic anemia (idiosyncratic)
• Antibody-mediated myasthenia gravis and Lambert–Eaton myasthenic syndrome, which may persist even after its withdrawal
• Drug-induced systemic lupus erythematosus
• Elastosis perforans serpiginosa
  (2025). 9781416029991, Elsevier. ISBN 9781416029991
• Toxic Myopathy
  (2025). 9780443068898, Elsevier Limited. ISBN 9780443068898
• Unwanted breast growth (macromastia)
• Oligospermia

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Chemistry

Penicillamine is a trifunctional group organic compound, consisting of a thiol, an amine, and a carboxylic acid. It is an amino acid structurally similar to cysteine, but with geminal dimethyl α to the thiol. Like most amino acids, it is a colorless solid that exists in the form at physiological pH.

Penicillamine is a chiral molecule with one stereogenic center; the two have distinct physiological effects. (, having (–) optical rotation) is used as aa drug (a chiral drug). (, having (+) optical rotation) is toxic because it inhibits the action of pyridoxine (also known as vitamin B₆).

(2025). 9780080932941, Elsevier Science. . ISBN 9780080932941

is a metabolite of penicillin but has no antibiotic properties itself. A variety of penicillamine–copper complexes are known.

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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.

Penicillamine was first synthesized by John Cornforth under supervision of Robert Robinson.

(2025). 9781438118826, Infobase Publishing. . ISBN 9781438118826

Penicillamine has been used in rheumatoid arthritis since the first successful case in 1964.

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External links

Categories: Alpha-amino Acids, Antirheumatic Products, Chelating Agents, Enantiopure Drugs, Human Drug Metabolites, Nephrotoxins, Non-proteinogenic Amino Acids, Thiols, World Health Organization Essential Medicines, Wikipedia Medicine Articles Ready To Translate, Disease-modifying Antirheumatic Drugs

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