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Identification
NamePenicillamine
Accession NumberDB00859  (APRD01171)
TypeSmall Molecule
GroupsApproved
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.

Structure
Thumb
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
PA
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cupriminecapsule125 mgoralMerck Canada Inc1980-12-312005-06-18Canada
Cupriminecapsule250 mgoralValeant Canada Lp Valeant Canada S.E.C.1964-12-31Not applicableCanada
Cupriminecapsule250 mg/1oralAton Pharma, Inc.1970-12-04Not applicableUs
Depentablet250 mg/1oralMeda Pharmaceuticals Inc.1978-11-30Not applicableUs
Depen Tab 250mgtablet250 mgoralCarter Horner Corp.1981-12-312003-08-19Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AtamirSandoz
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIGNN1DV99GX
CAS number52-67-5
WeightAverage: 149.211
Monoisotopic: 149.051049291
Chemical FormulaC5H11NO2S
InChI KeyVVNCNSJFMMFHPL-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][C@](N)(C(O)=O)C(C)(C)S
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as l-alpha-amino acids. These are alpha amino acids which have the L-configuration of the alpha-carbon atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentL-alpha-amino acids
Alternative Parents
Substituents
  • L-alpha-amino acid
  • Methyl-branched fatty acid
  • Thia fatty acid
  • Branched fatty acid
  • Amino fatty acid
  • Fatty acyl
  • Fatty acid
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Alkylthiol
  • Hydrocarbon derivative
  • Primary amine
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Pharmacology
IndicationFor treatment of Wilson's disease, cystinuria and active rheumatoid arthritis.
PharmacodynamicsPenicillamine 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. It works by reducing numbers of T-lymphocytes, inhibiting macrophage function, decreasing IL-1, decreasing rheumatoid factor, and preventing collagen from cross-linking. Its use in Wilson's disease, a rare genetic disorder of copper metabolism, relies on its binding to accumulated copper and elimination through urine.
Mechanism of actionPenicillamine 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.
Related Articles
Absorptionrapidly but incompletely
Volume of distributionNot Available
Protein binding>80% (bound to plasma proteins)
Metabolism

Hepatic

Route of eliminationExcretion is mainly renal, mainly as disulfides.
Half life1 hour
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9278
Blood Brain Barrier+0.5821
Caco-2 permeable-0.7778
P-glycoprotein substrateNon-substrate0.7679
P-glycoprotein inhibitor INon-inhibitor0.9818
P-glycoprotein inhibitor IINon-inhibitor0.9959
Renal organic cation transporterNon-inhibitor0.9744
CYP450 2C9 substrateNon-substrate0.776
CYP450 2D6 substrateNon-substrate0.8636
CYP450 3A4 substrateNon-substrate0.7038
CYP450 1A2 substrateInhibitor0.8476
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9528
CYP450 2C19 inhibitorNon-inhibitor0.9187
CYP450 3A4 inhibitorNon-inhibitor0.9107
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9693
Ames testAMES toxic0.6358
CarcinogenicityNon-carcinogens0.6495
BiodegradationNot ready biodegradable0.8739
Rat acute toxicity2.0294 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9987
hERG inhibition (predictor II)Non-inhibitor0.962
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Aton pharma inc
  • Meda pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Capsuleoral125 mg
Capsuleoral250 mg
Capsuleoral250 mg/1
Tabletoral250 mg/1
Tabletoral250 mg
Prices
Unit descriptionCostUnit
Penicillamine(d-) powder8.88USD g
Cuprimine 250 mg capsule5.63USD capsule
Depen 250 mg titratab4.73USD tablet
Penicillamine powder2.81USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point198.5 °CPhysProp
water solubility1.11E+005 mg/L (at 20 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-1.78HANSCH,C ET AL. (1995)
logS-0.13ADME Research, USCD
pKa1.8MERCK for CO; NH2-7.9; thiol-10.5
Predicted Properties
PropertyValueSource
Water Solubility4.65 mg/mLALOGPS
logP-1.7ALOGPS
logP-2.1ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)2.56ChemAxon
pKa (Strongest Basic)9.09ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area63.32 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity37.23 m3·mol-1ChemAxon
Polarizability14.76 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (7.76 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Manfred Klaus Joachim Bock, deceased, “Method of producing penicillamine.” U.S. Patent US3968154, issued November, 1960.

US3968154
General References
  1. WALSHE JM: Penicillamine, a new oral therapy for Wilson's disease. Am J Med. 1956 Oct;21(4):487-95. [PubMed:13362281 ]
  2. Walshe JM: The story of penicillamine: a difficult birth. Mov Disord. 2003 Aug;18(8):853-9. [PubMed:12889074 ]
  3. Gong Y, Frederiksen SL, Gluud C: D-penicillamine for primary biliary cirrhosis. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004789. [PubMed:15495127 ]
  4. Suarez-Almazor ME, Spooner C, Belseck E: Penicillamine for rheumatoid arthritis. Cochrane Database Syst Rev. 2000;(2):CD001460. [PubMed:10796440 ]
  5. Munro R, Capell HA: Penicillamine. Br J Rheumatol. 1997 Jan;36(1):104-9. [PubMed:9117147 ]
External Links
ATC CodesM01CC01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (264 KB)
MSDSDownload (71.7 KB)
Interactions
Drug Interactions
Drug
Aluminum hydroxideThe serum concentration of Penicillamine can be decreased when it is combined with Aluminum hydroxide.
Calcium carbonateThe serum concentration of Penicillamine can be decreased when it is combined with Calcium carbonate.
DigoxinThe serum concentration of Digoxin can be decreased when it is combined with Penicillamine.
Ferric CitrateFerric Citrate can cause a decrease in the absorption of Penicillamine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Iron DextranIron Dextran can cause a decrease in the absorption of Penicillamine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium hydroxideThe serum concentration of Penicillamine can be decreased when it is combined with Magnesium hydroxide.
Magnesium oxideThe serum concentration of Penicillamine can be decreased when it is combined with Magnesium oxide.
PolaprezincThe serum concentration of Penicillamine can be decreased when it is combined with Polaprezinc.
Sodium bicarbonateThe serum concentration of Penicillamine can be decreased when it is combined with Sodium bicarbonate.
Food Interactions
  • Drink liberally.
  • Food reduces availability, take on an empty stomach.

Targets

Kind
Small molecule
Organism
Human
Pharmacological action
yes
Actions
chelator
References
  1. 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
Human
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, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
References
  1. 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 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23