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

Details

Stereochemistry ABSOLUTE
Molecular Formula C5H11NO2S.ClH
Molecular Weight 185.6735
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PENICILLAMINE HYDROCHLORIDE

SMILES

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

InChI

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

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.4609
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

2.9116801E10
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

2.9116801E10
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

2.9116801E10
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 (max)
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources: Page: p.1200
unhealthy, 45+/-12
n = 66
Health Status: unhealthy
Condition: Diffuse systemic sclerosis
Age Group: 45+/-12
Sex: M+F
Population Size: 66
Sources: Page: p.1200
Disc. AE: Proteinuria, Rash...
AEs leading to
discontinuation/dose reduction:
Proteinuria (10.6%)
Rash
Myasthenia gravis (1.5%)
Thrombocytopenia
Flu-like illness
Stomatitis
Sources: Page: p.1200
4 g 1 times / day multiple, oral (max)
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Wilson's disease|Cystinuria
Sources: Page: p.4
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: Page: p.4
AEs

AEs

AESignificanceDosePopulation
Myasthenia gravis 1.5%
Disc. AE
1 g 1 times / day multiple, oral (max)
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources: Page: p.1200
unhealthy, 45+/-12
n = 66
Health Status: unhealthy
Condition: Diffuse systemic sclerosis
Age Group: 45+/-12
Sex: M+F
Population Size: 66
Sources: Page: p.1200
Proteinuria 10.6%
Disc. AE
1 g 1 times / day multiple, oral (max)
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources: Page: p.1200
unhealthy, 45+/-12
n = 66
Health Status: unhealthy
Condition: Diffuse systemic sclerosis
Age Group: 45+/-12
Sex: M+F
Population Size: 66
Sources: Page: p.1200
Flu-like illness Disc. AE
1 g 1 times / day multiple, oral (max)
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources: Page: p.1200
unhealthy, 45+/-12
n = 66
Health Status: unhealthy
Condition: Diffuse systemic sclerosis
Age Group: 45+/-12
Sex: M+F
Population Size: 66
Sources: Page: p.1200
Rash Disc. AE
1 g 1 times / day multiple, oral (max)
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources: Page: p.1200
unhealthy, 45+/-12
n = 66
Health Status: unhealthy
Condition: Diffuse systemic sclerosis
Age Group: 45+/-12
Sex: M+F
Population Size: 66
Sources: Page: p.1200
Stomatitis Disc. AE
1 g 1 times / day multiple, oral (max)
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources: Page: p.1200
unhealthy, 45+/-12
n = 66
Health Status: unhealthy
Condition: Diffuse systemic sclerosis
Age Group: 45+/-12
Sex: M+F
Population Size: 66
Sources: Page: p.1200
Thrombocytopenia Disc. AE
1 g 1 times / day multiple, oral (max)
Recommended
Dose: 1 g, 1 times / day
Route: oral
Route: multiple
Dose: 1 g, 1 times / day
Sources: Page: p.1200
unhealthy, 45+/-12
n = 66
Health Status: unhealthy
Condition: Diffuse systemic sclerosis
Age Group: 45+/-12
Sex: M+F
Population Size: 66
Sources: Page: p.1200
Leukopenia 5%
Disc. AE
4 g 1 times / day multiple, oral (max)
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Wilson's disease|Cystinuria
Sources: Page: p.4
Thrombocytopenia 5%
Disc. AE
4 g 1 times / day multiple, oral (max)
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Wilson's disease|Cystinuria
Sources: Page: p.4
Glomerulonephritis membranous Disc. AE
4 g 1 times / day multiple, oral (max)
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Wilson's disease|Cystinuria
Sources: Page: p.4
Hematuria Disc. AE
4 g 1 times / day multiple, oral (max)
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Wilson's disease|Cystinuria
Sources: Page: p.4
Myasthenia gravis Disc. AE
4 g 1 times / day multiple, oral (max)
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Wilson's disease|Cystinuria
Sources: Page: p.4
Nephrotic syndrome Disc. AE
4 g 1 times / day multiple, oral (max)
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Wilson's disease|Cystinuria
Sources: Page: p.4
Pemphigus foliaceus Disc. AE
4 g 1 times / day multiple, oral (max)
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Wilson's disease|Cystinuria
Sources: Page: p.4
Pemphigus vulgaris Disc. AE
4 g 1 times / day multiple, oral (max)
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Wilson's disease|Cystinuria
Sources: Page: p.4
Proteinuria Disc. AE
4 g 1 times / day multiple, oral (max)
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Wilson's disease|Cystinuria
Sources: Page: p.4
Goodpasture's syndrome rare
Disc. AE
4 g 1 times / day multiple, oral (max)
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Wilson's disease|Cystinuria
Sources: Page: p.4
Obliterative bronchiolitis rare
Disc. AE
4 g 1 times / day multiple, oral (max)
Recommended
Dose: 4 g, 1 times / day
Route: oral
Route: multiple
Dose: 4 g, 1 times / day
Sources: Page: p.4
unhealthy
Health Status: unhealthy
Condition: Wilson's disease|Cystinuria
Sources: Page: p.4
PubMed

PubMed

TitleDatePubMed
[Myasthenia gravis and autoimmune thyroiditis during the treatment of rheumatoid polyarthritis withD-penicillamine. Anatomoclinical study of 1 case].
1976 Oct
[Extra-capillary glomerulonephritis induced by D-penicillamine therapy].
1999 Apr 3
[D-penicillamine-induced pemphigus, polymyositis and myasthenia].
1999 Feb
Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies.
2000 Feb
Nitric oxide in the afferent synaptic transmission of the axolotl vestibular system.
2001
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
Cyclooxygenase-2 protein and prostaglandin E(2) production are up-regulated in a rat bladder inflammation model.
2001 Apr 13
Treatment of Wilson's disease: what are the relative roles of penicillamine, trientine, and zinc supplementation?
2001 Feb
Coexistence of zinc and iron augmented oxidative injuries in the nigrostriatal dopaminergic system of SD rats.
2001 Feb 1
Role of copper ions and cytochrome P450 in the vasodilator actions of the nitroxyl anion generator, Angeli's salt, on rat aorta.
2001 Feb 2
Nitric oxide attenuates H(2)O(2)-induced endothelial barrier dysfunction: mechanisms of protection.
2001 Jan
Estradiol-induced attenuation of pulmonary hypertension is not associated with altered eNOS expression.
2001 Jan
Cyclic AMP regulates the calcium transients released from IP(3)-sensitive stores by activation of rat kappa-opioid receptors expressed in CHO cells.
2001 Jan
Nitric oxide regulates smooth-muscle-specific myosin heavy chain gene expression at the transcriptional level-possible role of SRF and YY1 through CArG element.
2001 Jan
The regulation of NMDA-evoked dopamine release by nitric oxide in the frontal cortex and raphe nuclei of the freely moving rat.
2001 Jan 19
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
Transport of opioids from the brain to the periphery by P-glycoprotein: peripheral actions of central drugs.
2001 Mar
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
The role of delta-opioid receptor subtypes in neuropathic pain.
2001 Mar 9
Scleroderma in a child after chemotherapy for cancer.
2001 Mar-Apr
Glutamate release via NO production evoked by NMDA in the NTS enhances hypotension and bradycardia in vivo.
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. Wilson's Disease: In the absence of any drug reaction, a dose between 0.75 and 1.5 g that results in an initial 24-hour cupriuresis of over 2 mg should be continued for about three months, by which time the most reliable method of monitoring maintenance treatment is the determination of free copper in the serum. In patients who cannot tolerate as much as 1 g/day initially, initiating dosage with 250 mg/day, and increasing gradually to the requisite amount, gives closer control of the effects of the drug and may help to reduce the incidence of adverse reactions. Cystinuria:The usual dosage of CUPRIMINE in the treatment of cystinuria is 2 g/day for adults, with a range of 1 to 4 g/day. For pediatric patients, dosage can be based on 30 mg/kg/day. The total daily amount should be divided into four doses. If four equal doses are not feasible, give the larger portion at bedtime. If adverse reactions necessitate a reduction in dosage, it is important to retain the bedtime dose.
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 Sat Jun 26 14:34:45 UTC 2021
Edited
by admin
on Sat Jun 26 14:34:45 UTC 2021
Record UNII
5N9JK529ZJ
Record Status Validated (UNII)
Record Version
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Name Type Language
PENICILLAMINE HYDROCHLORIDE
MI   WHO-DD  
Systematic Name English
(S)-3,3-DIMETHYLCYSTEINE HYDROCHLORIDE
Systematic Name English
3-MERCAPTO-D-VALINE HYDROCHLORIDE
Systematic Name English
PENICILLAMINE HYDROCHLORIDE [WHO-DD]
Common Name English
PENICILLAMINE HYDROCHLORIDE [MI]
Common Name English
PEMINE
Brand Name English
Code System Code Type Description
PUBCHEM
92173
Created by admin on Sat Jun 26 14:34:45 UTC 2021 , Edited by admin on Sat Jun 26 14:34:45 UTC 2021
PRIMARY
FDA UNII
5N9JK529ZJ
Created by admin on Sat Jun 26 14:34:45 UTC 2021 , Edited by admin on Sat Jun 26 14:34:45 UTC 2021
PRIMARY
CAS
2219-30-9
Created by admin on Sat Jun 26 14:34:45 UTC 2021 , Edited by admin on Sat Jun 26 14:34:45 UTC 2021
PRIMARY
MERCK INDEX
M8467
Created by admin on Sat Jun 26 14:34:45 UTC 2021 , Edited by admin on Sat Jun 26 14:34:45 UTC 2021
PRIMARY Merck Index
ECHA (EC/EINECS)
218-727-9
Created by admin on Sat Jun 26 14:34:45 UTC 2021 , Edited by admin on Sat Jun 26 14:34:45 UTC 2021
PRIMARY
EVMPD
SUB03676MIG
Created by admin on Sat Jun 26 14:34:45 UTC 2021 , Edited by admin on Sat Jun 26 14:34:45 UTC 2021
PRIMARY
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