Penicillamine, sold under the brand name ofCuprimine among others, is amedication primarily used for the treatment ofWilson's disease.^[1] It is also used for people withkidney stones who havehigh urine cystine levels,rheumatoid arthritis, and variousheavy metal poisonings.^[1][2] It is taken by mouth.^[2]

Penicillamine

Clinical data
Trade names	Cuprimine, Cuprenyl, Depen, others
Other names	D-penicillamine (–)-penicillamine
AHFS/Drugs.com	Monograph
MedlinePlus	a618021
License data	US DailyMed: Penicillamine
Pregnancy category	AU: D
Routes of administration	By mouth (capsules)
ATC code	M01CC01 (WHO)
Legal status
Legal status	US:℞-only In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	Variable
Metabolism	Liver
Eliminationhalf-life	1 hour
Excretion	Kidney
Identifiers
IUPAC name (2S)-2-amino-3-methyl-3-sulfanylbutanoic acid
CAS Number	52-67-5 Y
PubChemCID	5852
IUPHAR/BPS	7264
DrugBank	DB00859 Y
ChemSpider	5643 Y
UNII	GNN1DV99GX
KEGG	D00496 Y
ChEBI	CHEBI:7959 Y
ChEMBL	ChEMBL1430 Y
CompTox Dashboard(EPA)	DTXSID6037069
ECHA InfoCard	100.000.136
Chemical and physical data
Formula	C5H11NO2S
Molar mass	149.21 g·mol−1
3D model (JSmol)	Interactive image
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
(verify)

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

It is used as a chelating agent:

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

Incystinuria, a hereditary disorder in which high urine cystine levels lead to the formation ofcystine stones, penicillamine binds with cysteine to yield a mixeddisulfide which is moresoluble than cystine.^[8]

Penicillamine has been used to treatscleroderma.^[9]

Penicillamine can be used as adisease-modifying antirheumatic drug (DMARD) to treat severe active rheumatoid arthritis in patients who have failed to respond to an adequate trial of conventional therapy,^[10] although it is rarely used today due to availability ofTNF inhibitors and other agents, such astocilizumab andtofacitinib. Penicillamine works by reducing numbers ofT-lymphocytes, inhibitingmacrophage function, decreasingIL-1, decreasingrheumatoid factor, and preventingcollagen from cross-linking.

Common side effects include rash, loss of appetite, nausea, diarrhea, andlow white blood cell levels.^[1] Other serious side effects includeliver problems,obliterative bronchiolitis, andmyasthenia gravis.^[1] It is not recommended in people withlupus erythematosus.^[2] Use duringpregnancy may result in harm to the baby.^[2] Penicillamine works bybinding heavy metals; the resulting penicillamine–metal complexes are then removed from the body in theurine.^[1]

Bone marrow suppression,dysgeusia,anorexia,vomiting, anddiarrhea are the most commonside effects, occurring in ~20–30% of the patients treated with penicillamine.^[11][12]

Other possible adverse effects include:

• Nephropathy^[8][11]
• Hepatotoxicity^[13]
• Membranous glomerulonephritis^[14]
• Aplastic anemia (idiosyncratic)^[13]
• Antibody-mediatedmyasthenia gravis^[11] andLambert–Eaton myasthenic syndrome, which may persist even after its withdrawal
• Drug-inducedsystemic lupus erythematosus^[15]
• Elastosis perforans serpiginosa^[16]
• Toxicmyopathies^[17]
• Unwanted breast growth (macromastia)^[18]
• Oligospermia

Penicillamine is a trifunctional organic compound, consisting of athiol, anamine, and acarboxylic acid. It is anamino acid structurally similar tocysteine, but withgeminal dimethylsubstituents α to the thiol. Like most amino acids, it is a colorless solid that exists in thezwitterionic form atphysiological pH.

Penicillamine is achiral molecule with onestereogenic center; the twoenantiomers have distinctphysiological effects.(S)-penicillamine (D-penicillamine, having (–)optical rotation) is used as aa drug (achiral drug).^[19](R)-penicillamine (L-penicillamine, having (+) optical rotation) is toxic because it inhibits the action ofpyridoxine (also known asvitamin B₆).^[20]D-penicillamine is ametabolite ofpenicillin but has noantibiotic properties itself. A variety of penicillamine–copper complexes are known.^[21]

John Walshe first described the use of penicillamine in Wilson's disease in 1956.^[22] He had discovered the compound in the urine of patients (including himself) who had takenpenicillin, and experimentally confirmed that it increased urinary copper excretion bychelation. 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 thatdimercaprol should be used as a chelator. Later studies confirmed both the copper-centered theory and the efficacy ofD-penicillamine. Walshe also pioneered other chelators in Wilson's such astriethylene tetramine andtetrathiomolybdate.^[23]

Penicillamine was first synthesized byJohn Cornforth under supervision ofRobert Robinson.^[24]

Penicillamine has been used in rheumatoid arthritis since the first successful case in 1964.^[25]

• "Penicillamine".Drug Information Portal. U.S. National Library of Medicine.