U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C5H11NO2S
Molecular Weight 149.2126
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PENICILLAMINE

SMILES

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

InChI

InChIKey=VVNCNSJFMMFHPL-VKHMYHEASA-N
InChI=1S/C5H11NO2S/c1-5(2,9)3(6)4(7)8/h3,9H,6H2,1-2H3,(H,7,8)/t3-/m0/s1

HIDE SMILES / InChI

Molecular Formula C5H11NO2S
Molecular Weight 149.2126
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Penicillamine, sold under the trade names of Cuprimine among others, is a medication primarily used for treatment of Wilson's disease, cystinuria and active rheumatoid arthritis. Penicillamine is a chelating agent recommended for the removal of excess copper in patients with Wilson's disease. From in vitro studies which indicate that one atom of copper combines with two molecules of penicillamine. Penicillamine also reduces excess cystine excretion in cystinuria. This is done, at least in part, by disulfide interchange between penicillamine and cystine, resulting in formation of penicillamine-cysteine disulfide, a substance that is much more soluble than cystine and is excreted readily. Penicillamine interferes with the formation of cross-links between tropocollagen molecules and cleaves them when newly formed. The mechanism of action of penicillamine in rheumatoid arthritis is unknown although it appears to suppress disease activity. Unlike cytotoxic immunosuppressants, penicillamine markedly lowers IgM rheumatoid factor but produces no significant depression in absolute levels of serum immunoglobulins. Also unlike cytotoxic immunosuppressants which act on both, penicillamine in vitro depresses T-cell activity but not B-cell activity.

Originator

Curator's Comment:: John Walshe first described the use of penicillamine in Wilson's disease in 1956.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CUPRIMINE

Approved Use

CUPRIMINE is indicated in the treatment of Wilson's disease, cystinuria, and in patients with severe, active rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy.

Launch Date

29116800000
Primary
CUPRIMINE

Approved Use

CUPRIMINE is indicated in the treatment of Wilson's disease, cystinuria, and in patients with severe, active rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy.

Launch Date

29116800000
Primary
CUPRIMINE

Approved Use

CUPRIMINE is indicated in the treatment of Wilson's disease, cystinuria, and in patients with severe, active rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy.

Launch Date

29116800000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5.36 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENICILLAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
8.04 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENICILLAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
73.19 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENICILLAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
83.97 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENICILLAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.37 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENICILLAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
5.01 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENICILLAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
1 g 1 times / day multiple, oral
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources:
unhealthy, 45+/-12
Health Status: unhealthy
Age Group: 45+/-12
Sex: M+F
Sources:
Disc. AE: Proteinuria, Rash...
AEs leading to
discontinuation/dose reduction:
Proteinuria (10.6%)
Rash
Myasthenia gravis (1.5%)
Thrombocytopenia
Flu-like illness
Stomatitis
Sources:
4 g 1 times / day multiple, oral
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources:
unhealthy
Disc. AE: Leukopenia, Thrombocytopenia...
AEs leading to
discontinuation/dose reduction:
Leukopenia (5%)
Thrombocytopenia (5%)
Proteinuria
Hematuria
Glomerulonephritis membranous
Nephrotic syndrome
Goodpasture's syndrome (rare)
Obliterative bronchiolitis (rare)
Myasthenia gravis
Pemphigus vulgaris
Pemphigus foliaceus
Sources:
AEs

AEs

AESignificanceDosePopulation
Myasthenia gravis 1.5%
Disc. AE
1 g 1 times / day multiple, oral
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources:
unhealthy, 45+/-12
Health Status: unhealthy
Age Group: 45+/-12
Sex: M+F
Sources:
Proteinuria 10.6%
Disc. AE
1 g 1 times / day multiple, oral
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources:
unhealthy, 45+/-12
Health Status: unhealthy
Age Group: 45+/-12
Sex: M+F
Sources:
Flu-like illness Disc. AE
1 g 1 times / day multiple, oral
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources:
unhealthy, 45+/-12
Health Status: unhealthy
Age Group: 45+/-12
Sex: M+F
Sources:
Rash Disc. AE
1 g 1 times / day multiple, oral
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources:
unhealthy, 45+/-12
Health Status: unhealthy
Age Group: 45+/-12
Sex: M+F
Sources:
Stomatitis Disc. AE
1 g 1 times / day multiple, oral
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources:
unhealthy, 45+/-12
Health Status: unhealthy
Age Group: 45+/-12
Sex: M+F
Sources:
Thrombocytopenia Disc. AE
1 g 1 times / day multiple, oral
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources:
unhealthy, 45+/-12
Health Status: unhealthy
Age Group: 45+/-12
Sex: M+F
Sources:
Leukopenia 5%
Disc. AE
4 g 1 times / day multiple, oral
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources:
unhealthy
Thrombocytopenia 5%
Disc. AE
4 g 1 times / day multiple, oral
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources:
unhealthy
Glomerulonephritis membranous Disc. AE
4 g 1 times / day multiple, oral
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources:
unhealthy
Hematuria Disc. AE
4 g 1 times / day multiple, oral
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources:
unhealthy
Myasthenia gravis Disc. AE
4 g 1 times / day multiple, oral
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources:
unhealthy
Nephrotic syndrome Disc. AE
4 g 1 times / day multiple, oral
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources:
unhealthy
Pemphigus foliaceus Disc. AE
4 g 1 times / day multiple, oral
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources:
unhealthy
Pemphigus vulgaris Disc. AE
4 g 1 times / day multiple, oral
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources:
unhealthy
Proteinuria Disc. AE
4 g 1 times / day multiple, oral
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources:
unhealthy
Goodpasture's syndrome rare
Disc. AE
4 g 1 times / day multiple, oral
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources:
unhealthy
Obliterative bronchiolitis rare
Disc. AE
4 g 1 times / day multiple, oral
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources:
unhealthy
PubMed

PubMed

TitleDatePubMed
Myasthenia gravis associated with penicillamine treatment for rheumatoid arthritis.
1975 Mar 15
Drug treatment of scleroderma.
2001
D-Penicillamine for preventing retinopathy of prematurity in preterm infants.
2001
Nitric oxide in the afferent synaptic transmission of the axolotl vestibular system.
2001
Nitric oxide differentially regulates induction of type II nitric oxide synthase in rat vascular smooth muscle cells versus macrophages.
2001 Apr
Divergent effects of ischemia/reperfusion and nitric oxide donor on TNFalpha mRNA accumulation in rat organs.
2001 Apr
Modulation of human platelet aggregation by the phosphodiesterase type 5 inhibitor sildenafil.
2001 Apr
NMDA-induced phosphorylation of the microtubule-associated protein MAP-2 is mediated by activation of nitric oxide synthase and MAP kinase.
2001 Apr
Effects of nitrovasodilators on the human fetal-placental circulation in vitro.
2001 Apr
NF-kappaB stimulates inducible nitric oxide synthase to protect mouse hepatocytes from TNF-alpha- and Fas-mediated apoptosis.
2001 Apr
Activity of mu- and delta-opioid agonists in vas deferens from mice deficient in MOR gene.
2001 Apr
Galpha(14) links a variety of G(i)- and G(s)-coupled receptors to the stimulation of phospholipase C.
2001 Apr
Interaction of co-expressed mu- and delta-opioid receptors in transfected rat pituitary GH(3) cells.
2001 Apr
Opposing actions of nitric oxide on synaptic inputs of identified interneurones in the central nervous system of the crayfish.
2001 Apr
Induction of a non-rhythmic motor pattern by nitric oxide in hatchling Rana temporaria embryos.
2001 Apr
Nitric oxide increases fluid extravasation from the splenic circulation of the rat.
2001 Apr
Effect of NO donors on protein phosphorylation in intact vascular and nonvascular smooth muscles.
2001 Apr
Direct autocrine inhibition and cAMP-dependent potentiation of single L-type Ca2+ channels in bovine chromaffin cells.
2001 Apr 1
Cyclooxygenase-2 protein and prostaglandin E(2) production are up-regulated in a rat bladder inflammation model.
2001 Apr 13
Enantiomeric analysis of pharmaceutical compounds by ion/molecule reactions.
2001 Apr 15
Effect of nitric oxide on basal and stretch-induced release of atrial natriuretic factor (ANF) from isolated perfused rat atria.
2001 Apr 20
Uptake and efflux of the peptidic delta-opioid receptor agonist.
2001 Apr 6
The effect of various capacitation active compounds and capacitation time on the in vitro fertility and protein tyrosine phosphorylation profiles of bovine sperm.
2001 Feb
Nitric oxide inhibits norepinephrine stimulated contraction of human internal thoracic artery and rat aorta.
2001 Feb
Superoxide inhibits neuronal nitric oxide synthase influences on afferent arterioles in spontaneously hypertensive rats.
2001 Feb
Pharmacological effects of naltriben as a ligand for opioid mu and kappa receptors in rat cerebral cortex.
2001 Feb 2
Ligand binding profiles of delta-opioid receptor in human cerebral cortex membranes: evidence of delta-opioid receptor heterogeneity.
2001 Feb 23
Ionophoretic studies on mixed metal--nitrilotriacetate--penicillamine complexes.
2001 Feb 23
[Induction of nitric oxide synthesis in mononuclear cells in culture using peritoneal fluid from women with endometriosis, in relation to the percentage of T lymphocytes and NK cells identified in an such environment].
2001 Jan
Metabolic regulation of aldose reductase activity by nitric oxide donors.
2001 Jan 30
[Drug-induced taste disorders: analysis of the French Pharmacovigilance Database and literature review].
2001 Jan-Feb
Stimulation by nitric oxide of gastric acid secretion in bullfrog fundic mucosa in vitro.
2001 Mar
Involvement of cyclooxygenase-derived prostaglandin E2 and nitric oxide in the protection of rat pancreas afforded by low dose of lipopolysaccharide.
2001 Mar
The Disability Index of the Health Assessment Questionnaire is a predictor and correlate of outcome in the high-dose versus low-dose penicillamine in systemic sclerosis trial.
2001 Mar
Coincident signalling between the Gi/Go-coupled delta-opioid receptor and the Gq-coupled m3 muscarinic receptor at the level of intracellular free calcium in SH-SY5Y cells.
2001 Mar
Transport of opioids from the brain to the periphery by P-glycoprotein: peripheral actions of central drugs.
2001 Mar
IL-4 gene expression up-regulated by mercury in rat mast cells: a role of oxidant stress in IL-4 transcription.
2001 Mar
Expression of functional mu-opioid receptors during T cell development.
2001 Mar 1
Tissue plasminogen activator protects hippocampal neurons from oxygen-glucose deprivation injury.
2001 Mar 1
L-arginine effects on Na+ transport in M-1 mouse cortical collecting duct cells--a cationic amino acid absorbing epithelium.
2001 Mar 15
Effect of redox modulation on xenogeneic target cells: the combination of nitric oxide and thiol deprivation protects porcine endothelial cells from lysis by IL-2-activated human NK cells.
2001 Mar 15
Nitric oxide augments voltage-activated calcium currents of crustacea (Idotea baltica) skeletal muscle.
2001 Mar 16
The metabolic evidence of synergistic interaction between DAMGO and DPDPE on undifferentiated SH-SY5Y cells.
2001 Mar 26
Cyclooxygenase-1 participates in selected vasodilator responses of the cerebral circulation.
2001 Mar 30
Evidence for an endocannabinoid system in the central nervous system of the leech Hirudo medicinalis.
2001 Mar 5
Scleroderma in a child after chemotherapy for cancer.
2001 Mar-Apr
Old and new drugs used in rheumatoid arthritis: a historical perspective. Part 1: the older drugs.
2001 Mar-Apr
Nitric oxide reduces energy supply by direct action on the respiratory chain in isolated cardiomyocytes.
2001 May
Glutamate release via NO production evoked by NMDA in the NTS enhances hypotension and bradycardia in vivo.
2001 May
Endothelial nitric oxide synthase plays an essential role in regulation of renal oxygen consumption by NO.
2001 May
Patents

Sample Use Guides

In all patients receiving penicillamine, it is important that CUPRIMINE be given on an empty stomach, at least one hour before meals or two hours after meals, and at least one hour apart from any other drug, food, or milk.
Route of Administration: Oral
Degradation of 2-deoxyribose mediated by 10 uM Cu(II) and 3 mM ascorbate was fully inhibited by 20 uM Penicillamine (d-penicillamine) (I50 = 10 uM) in vitro.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:05:25 UTC 2021
Edited
by admin
on Fri Jun 25 21:05:25 UTC 2021
Record UNII
GNN1DV99GX
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PENICILLAMINE
EP   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
PENICILLAMINE [VANDF]
Common Name English
PENICILLAMINE [USP MONOGRAPH]
Common Name English
PENICILLAMINE [EP]
Common Name English
PENICILLAMINE [USP-RS]
Common Name English
D-PENICILLAMINE
Systematic Name English
PENICILLAMINE [EP MONOGRAPH]
Common Name English
PENICILLAMINE [ORANGE BOOK]
Common Name English
CUPRIMINE
Brand Name English
D-3-MERCAPTOVALINE
Common Name English
PENICILLAMINE [MART.]
Common Name English
PENICILLAMINE [USAN]
Common Name English
PENICILLAMINE [HSDB]
Common Name English
PENICILLAMINE [INN]
Common Name English
PENICILLAMINE [MI]
Common Name English
NSC-81549
Code English
D-VALINE, 3-MERCAPTO-
Systematic Name English
DEPEN
Brand Name English
PENICILLAMINE [WHO-DD]
Common Name English
Classification Tree Code System Code
WHO-ESSENTIAL MEDICINES LIST 4.2
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
NDF-RT N0000175713
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
NCI_THESAURUS C1971
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 2.4
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
WHO-VATC QM01CC01
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
LIVERTOX 752
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
WHO-ATC M01CC01
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
Code System Code Type Description
CAS
52-67-5
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
DRUG BANK
DB00859
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-148-8
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
MERCK INDEX
M8467
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY Merck Index
USP_CATALOG
1501006
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY USP-RS
IUPHAR
7264
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
ChEMBL
CHEMBL1430
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
FDA UNII
GNN1DV99GX
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
EPA CompTox
52-67-5
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
NCI_THESAURUS
C729
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
PUBCHEM
5852
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
MESH
D010396
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
LACTMED
Penicillamine
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
WIKIPEDIA
PENICILLAMINE
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
HSDB
3378
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
INN
1121
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
EVMPD
SUB09667MIG
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
RXCUI
7975
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY RxNorm
EVMPD
SUB127001
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
DRUG CENTRAL
2081
Created by admin on Fri Jun 25 21:05:25 UTC 2021 , Edited by admin on Fri Jun 25 21:05:25 UTC 2021
PRIMARY
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BINDING
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