Penicillamine

Penicillamine

Systematic (IUPAC) name
(2S)-2-amino-3-methyl-3-sulfanylbutanoic acid
Clinical data
Trade names	Cuprimine
AHFS/Drugs.com	monograph
Pregnancy category	AU: D US: D (Evidence of risk)
Legal status	℞ (Prescription only)
Routes of administration	Oral
Pharmacokinetic data
Bioavailability	Variable
Metabolism	Hepatic
Biological half-life	1 hour
Excretion	Renal
Identifiers
CAS Number	52-67-5 Y
ATC code	M01CC01 (WHO)
PubChem	CID: 5852
IUPHAR/BPS	7264
DrugBank	DB00859 Y
ChemSpider	5643 Y
UNII	GNN1DV99GX Y
KEGG	D00496 Y
ChEBI	CHEBI:7959 Y
ChEMBL	CHEMBL1430 Y
Chemical data
Formula	C5H11NO2S
Molecular mass	149.212 g/mol
SMILES CC(C)([C@H](C(=O)O)N)S
InChI InChI=1S/C5H11NO2S/c1-5(2,9)3(6)4(7)8/h3,9H,6H2,1-2H3,(H,7,8)/t3-/m0/s1 Y Key:VVNCNSJFMMFHPL-VKHMYHEASA-N Y
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Penicillamine, sold under the trade names of Cuprimine and Depen, is a medication of the chelator class. It is D-penicillamine, as L-penicillamine is toxic (it inhibits the action of pyridoxine). It is an α-amino acid metabolite of penicillin, although it has no antibiotic properties.

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

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.

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.
• In cystinuria, a hereditary disorder featuring 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 was the second line treatment for arsenic poisoning, after dimercaprol (BAL). It is no longer recommended.
• Penicillamine can be used as DMARD (Disease-modifying antirheumatic drugs)

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:

• Nephropathy
• Hepatotoxicity
• Membranous glomerulonephritis
• 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
• Toxic myopathies
• Unwanted breast growth.

Despite the similar name, there is no cross sensitivity between penicillin and penicillamine. Those with penicillin allergies may take it safely.

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, 2HCl, and tetrathiomolybdate.

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

External links

• Penicillamine (Systemic) - Medlineplus.org
• Penicillamine and Arthritis - Medicinenet.com