Penicillamine
Identification
- Name
- Penicillamine
- Accession Number
- DB00859
- Description
Penicillamine is a pharmaceutical of the chelator class. The pharmaceutical form 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.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Penicillamine (DB00859)
- Weight
- Average: 149.211
Monoisotopic: 149.051049291 - Chemical Formula
- C5H11NO2S
- Synonyms
- (−)-penicillamine
- (S)-2-amino-3-mercapto-3-methylbutanoic acid
- (S)-3,3-dimethylcysteine
- 3-mercapto-D-valine
- D-(−)-penicillamine
- D-penicillamine
- D-β,β-dimethylcysteine
- penicilamina
- Penicillamine
- External IDs
- NSC-81549
Pharmacology
- Indication
For treatment of Wilson's disease, cystinuria and active rheumatoid arthritis.
- Associated Conditions
- Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- Pharmacodynamics
Penicillamine is a chelating agent used in the treatment of Wilson's disease. It is also used to reduce cystine excretion in cystinuria and to treat patients with severe, active rheumatoid arthritis unresponsive to conventional therapy. Penicillamine is used as a form of immunosuppression to treat rheumatoid arthritis. Penicillamine inhibits macrophages, decreases IL-1 and the number of T-lymphocytes, and prevents collagen cross linkage. In Wilson's disease it binds copper, allowing it to be eliminated in the urine.
- Mechanism of action
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.
Target Actions Organism ACopper chelatorHumans - Absorption
rapidly but incompletely
- Volume of distribution
- Not Available
- Protein binding
>80% (bound to plasma proteins)
- Metabolism
Hepatic
- Route of elimination
Excretion is mainly renal, mainly as disulfides.
- Half-life
1 hour
- Clearance
- Not Available
- Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More- Toxicity
- Not Available
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Unlock Additional DataAbatacept The risk or severity of adverse effects can be increased when Penicillamine is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Penicillamine. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Penicillamine. Acetylcysteine The excretion of Penicillamine can be decreased when combined with Acetylcysteine. Acetylsalicylic acid The risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Penicillamine. Acipimox The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Penicillamine is combined with Acipimox. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Penicillamine. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Penicillamine. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Penicillamine. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Penicillamine. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionAction
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more
- Food Interactions
- Drink plenty of fluids.
- Take on an empty stomach. Co-administration with food decreases bioavailability.
Products
- International/Other Brands
- Atamir (Sandoz)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Unlock Additional DataCuprimine Capsule 125 mg/1 Oral Merck Sharp & Dohme Limited 1970-12-04 2009-05-31 US 
Cuprimine Capsule 250 mg/1 Oral Bausch Health US, LLC 1970-12-04 Not applicable US Cuprimine Capsule 250 mg/1 Oral Merck Sharp & Dohme Limited 1970-12-04 2009-05-31 US Cuprimine Capsule 125 mg Oral Merck Ltd. 1980-12-31 2005-06-18 Canada 
Cuprimine Capsule Oral Bausch Health, Canada Inc. 1964-12-31 Not applicable Canada D-Penamine Tablet 125 mg/1 Oral Mylan Pharmaceuticals Inc. 2018-11-15 2020-06-30 US Depen Tablet 250 mg/1 Oral MEDA Pharmaceuticals 1978-11-30 Not applicable US Depen Tab 250mg Tablet Oral Carter Horner Corp. 1981-12-31 2003-08-19 Canada Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
Learn more
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Unlock Additional DataPenicillamine Capsule 250 1/1 Oral Apotex Corp. 2020-06-26 Not applicable US Penicillamine Capsule 250 mg/1 Oral Oceanside Pharmaceuticals 1970-12-04 Not applicable US Penicillamine Capsule 250 mg/1 Oral Actavis Pharma, Inc. 2019-06-25 Not applicable US Penicillamine Capsule 250 mg/1 Oral ANI Pharmaceuticals, Inc. 2019-05-07 Not applicable US Penicillamine Capsule 250 mg/1 Oral Par Pharmaceutical, Inc. 2020-01-08 Not applicable US Penicillamine Capsule, gelatin coated 250 mg/1 Oral Dr. Reddy's Laboratories Inc. 2020-08-04 Not applicable US Penicillamine Tablet, film coated 250 mg/1 Oral Par Pharmaceutical, Inc. 2020-01-02 Not applicable US Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
Learn more
- Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image D-Penamine Penicillamine (125 mg/1) Tablet Oral Mylan Pharmaceuticals Inc. 2018-11-15 2020-06-30 US
Categories
- ATC Codes
- M01CC01 — Penicillamine
- Drug Categories
- Agents Causing Muscle Toxicity
- Amino Acids
- Amino Acids, Peptides, and Proteins
- Amino Acids, Sulfur
- Antidotes
- Antiinflammatory and Antirheumatic Products
- Antirheumatic Agents
- Chelating Agents
- Compounds used in a research, industrial, or household setting
- Heavy Metal Antagonists
- Immunosuppressive Agents
- Musculo-Skeletal System
- Myelosuppressive Agents
- OATP1B1/SLCO1B1 Substrates
- Penicillamine and Similar Agents
- Protective Agents
- Sequestering Agents
- Specific Antirheumatic Agents
- Sulfur Compounds
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as valine and derivatives. These are compounds containing valine or a derivative thereof resulting from reaction of valine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Valine and derivatives
- Alternative Parents
- D-alpha-amino acids / Thia fatty acids / Methyl-branched fatty acids / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Alkylthiols / Organopnictogen compounds / Organic oxides / Monoalkylamines show 2 more
- Substituents
- Aliphatic acyclic compound / Alkylthiol / Alpha-amino acid / Amine / Amino acid / Branched fatty acid / Carbonyl group / Carboxylic acid / D-alpha-amino acid / Fatty acid show 15 more
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- penicillamine (CHEBI:7959)
Chemical Identifiers
- UNII
- GNN1DV99GX
- CAS number
- 52-67-5
- InChI Key
- VVNCNSJFMMFHPL-VKHMYHEASA-N
- InChI
- InChI=1S/C5H11NO2S/c1-5(2,9)3(6)4(7)8/h3,9H,6H2,1-2H3,(H,7,8)/t3-/m0/s1
- IUPAC Name
- (2S)-2-amino-3-methyl-3-sulfanylbutanoic acid
- SMILES
- [H][[email protected]](N)(C(O)=O)C(C)(C)S
References
- Synthesis Reference
Manfred Klaus Joachim Bock, deceased, "Method of producing penicillamine." U.S. Patent US3968154, issued November, 1960.
US3968154- General References
- WALSHE JM: Penicillamine, a new oral therapy for Wilson's disease. Am J Med. 1956 Oct;21(4):487-95. [PubMed:13362281]
- Walshe JM: The story of penicillamine: a difficult birth. Mov Disord. 2003 Aug;18(8):853-9. [PubMed:12889074]
- Gong Y, Frederiksen SL, Gluud C: D-penicillamine for primary biliary cirrhosis. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004789. [PubMed:15495127]
- Suarez-Almazor ME, Spooner C, Belseck E: Penicillamine for rheumatoid arthritis. Cochrane Database Syst Rev. 2000;(2):CD001460. [PubMed:10796440]
- Munro R, Capell HA: Penicillamine. Br J Rheumatol. 1997 Jan;36(1):104-9. [PubMed:9117147]
- External Links
- KEGG Drug
- D00496
- KEGG Compound
- C07418
- PubChem Compound
- 5852
- PubChem Substance
- 46508305
- ChemSpider
- 5643
- BindingDB
- 39346
- 7975
- ChEBI
- 7959
- ChEMBL
- CHEMBL1430
- ZINC
- ZINC000000114127
- Therapeutic Targets Database
- DNC000575
- PharmGKB
- PA450840
- PDBe Ligand
- LEI
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Penicillamine
- AHFS Codes
- 64:00.00 — Heavy Metal Antagonists
- PDB Entries
- 3h5g
- FDA label
- Download (264 KB)
- MSDS
- Download (71.7 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Cystine renal calculi 1 3 Active Not Recruiting Treatment Wilson's Disease 1 2 Completed Treatment Brain and Central Nervous System Tumors 1 2 Unknown Status Treatment Arteriovenous fistula occlusion 1 0 Recruiting Treatment Wilson's Disease 1 Not Available No Longer Available Not Available Scleroderma 1
Pharmacoeconomics
- Manufacturers
- Aton pharma inc
- Meda pharmaceuticals inc
- Packagers
- Aton Pharma Inc.
- Draxis Specialty Pharmaceuticals Inc.
- Gallipot
- Meda AB
- Medisca Inc.
- Merck & Co.
- Patheon Inc.
- Dosage Forms
Form Route Strength Capsule Oral 150 mg Capsule Oral 250 mg Capsule Oral Capsule 250 mg Capsule Oral 125 mg/1 Capsule Oral 125 mg Capsule Oral 250 mg/1 Capsule, coated Oral 250 mg Tablet Oral 125 mg/1 Tablet Oral 250 mg/1 Tablet Oral Capsule Oral 250 1/1 Capsule, gelatin coated Oral 250 mg/1 Powder Not applicable 1 g/1g Tablet, film coated Oral 250 mg/1 - Prices
Unit description Cost Unit Penicillamine(d-) powder 8.88USD g Cuprimine 250 mg capsule 5.63USD capsule Depen 250 mg titratab 4.73USD tablet Penicillamine powder 2.81USD g DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 198.5 °C PhysProp water solubility 1.11E+005 mg/L (at 20 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP -1.78 HANSCH,C ET AL. (1995) logS -0.13 ADME Research, USCD pKa 1.8 MERCK for CO; NH2-7.9; thiol-10.5 - Predicted Properties
Property Value Source Water Solubility 4.65 mg/mL ALOGPS logP -1.7 ALOGPS logP -2.1 ChemAxon logS -1.5 ALOGPS pKa (Strongest Acidic) 2.56 ChemAxon pKa (Strongest Basic) 9.09 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 63.32 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 37.22 m3·mol-1 ChemAxon Polarizability 14.76 Å3 ChemAxon Number of Rings 0 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9278 Blood Brain Barrier + 0.5821 Caco-2 permeable - 0.7778 P-glycoprotein substrate Non-substrate 0.7679 P-glycoprotein inhibitor I Non-inhibitor 0.9818 P-glycoprotein inhibitor II Non-inhibitor 0.9959 Renal organic cation transporter Non-inhibitor 0.9744 CYP450 2C9 substrate Non-substrate 0.776 CYP450 2D6 substrate Non-substrate 0.8636 CYP450 3A4 substrate Non-substrate 0.7038 CYP450 1A2 substrate Inhibitor 0.8476 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9528 CYP450 2C19 inhibitor Non-inhibitor 0.9187 CYP450 3A4 inhibitor Non-inhibitor 0.9107 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9693 Ames test AMES toxic 0.6358 Carcinogenicity Non-carcinogens 0.6495 Biodegradation Not ready biodegradable 0.8739 Rat acute toxicity 2.0294 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9987 hERG inhibition (predictor II) Non-inhibitor 0.962
Spectra
- Mass Spec (NIST)
- Download (7.76 KB)
- Spectra
Spectrum Spectrum Type Splash Key GC-MS Spectrum - GC-EI-TOF GC-MS splash10-0fr5-1930000000-6ee8522d7087601d49e6 GC-MS Spectrum - GC-EI-TOF GC-MS splash10-00di-9520000000-1ac6006c4f882c72292b GC-MS Spectrum - GC-EI-TOF GC-MS splash10-00di-9640000000-736237ccaaa4ef171daa Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
Yes
Chelator
References
- Brewer GJ: Novel therapeutic approaches to the treatment of Wilson's disease. Expert Opin Pharmacother. 2006 Feb;7(3):317-24. [PubMed:16448326]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- Gui C, Hagenbuch B: Role of transmembrane domain 10 for the function of organic anion transporting polypeptide 1B1. Protein Sci. 2009 Nov;18(11):2298-306. doi: 10.1002/pro.240. [PubMed:19760661]
Drug created on June 13, 2005 07:24 / Updated on October 21, 2020 01:55
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