Accession Number
Small Molecule
Approved, Investigational

Triethylenetatramine (TETA) is a highly selective divalent Cu(II) chelator and orphan drug that revereses copper overload in tissues. Its salt form, trientine (triethylenetetramine dihydrochloride or 2,2,2-tetramine) was introduced in 1969 as an alternative to D-penicillamine. It consists of a polyamine-like structure different from D-penicillamine, as it lack sulfhydryl groups. It was previously approved by FDA in 1985 as second-line pharmacotherapy for Wilson's disease. Although penicillamine treatment is believed to be more extensive, TETA therapy has been shown to be an effective initial therapy, even with patients with decompensated liver disease at the outset, and prolonged TETA treatment is not associated with adverse effects as expected in penicillamine treatment. Its clinical applications on cancer, diabetes mellitus, Alzheimer's disease and vascular demetia are being studied.

  • TETA
  • Trien
  • Trientine
Product Ingredients
IngredientUNIICASInChI Key
Trientine hydrochlorideHC3NX5458238260-01-4WYHIICXRPHEJKI-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SyprineCapsule250 mg/1OralBausch Health US LLC1985-11-08Not applicableUs
SyprineCapsule250 mg/1OralAton Pharma, Inc.1985-11-082016-08-26Us
SyprineCapsule250 mg/1OralMerck Sharp & Dohme Limited1985-11-082008-03-31Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Trientine hydrochlorideCapsule250 mg/1OralNovadoz Pharmaceuticals Llc2019-05-22Not applicableUs
Trientine hydrochlorideCapsule250 mg/1OralMsn Laboratories Private Limited2019-05-22Not applicableUs
Trientine hydrochlorideCapsule250 mg/1OralRising Pharmaceuticals, Inc.2020-02-20Not applicableUs
Trientine HydrochlorideCapsule, gelatin coated250 mg/1OralAmneal Pharmaceuticals NY LLC2019-02-08Not applicableUs
Trientine hydrochlorideCapsule250 mg/1OralCadila Healthcare Limited2019-04-29Not applicableUs
Trientine HydrochlorideCapsule250 mg/1OralKadmon Pharmaceuticals, LLC2019-09-30Not applicableUs
Trientine HydrochlorideCapsule250 mg/1OralDr.Reddys Laboratories Inc2019-07-03Not applicableUs
Trientine hydrochlorideCapsule250 mg/1OralZydus Pharmaceuticals (USA) Inc.2019-04-29Not applicableUs
Trientine HydrochlorideCapsule250 mg/1OralOceanside Pharmaceutials2018-02-09Not applicableUs
Trientine HydrochlorideCapsule250 mg/1OralNavinta Llc2019-03-01Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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CAS number
Average: 146.2339
Monoisotopic: 146.153146596
Chemical Formula
InChI Key



Trientine is a copper chelator used in the treatment of Wilson's disease as an alternative to D-penicillamine. It tends to be used in patients who are experiencing serious adverse effects from penicillamine therapy or intolerance of penicillamine.

Associated Conditions

TETA is a selective copper (II) chelator. tightly binds and facilitates systemic elimination of Cu(II) into the urine whilst neutralizing its catalytic activity, but does not cause systemic copper deficiency even after prolonged use. It may also act as an antioxidant as it suppresses the copper-mediated oxidative stress. TETA not only increases urinary Cu excretion, but also decreases intestinal copper absorption by 80%.

Mechanism of action

Copper is chelated by forming a stable complex with the four constituent nitrogens in a planar ring as copper displays enhanced ligand binding properties for nitrogen compared to oxygen. It binds Cu(II) very tightly, having a dissociation constant from Cu(II) of 10^−15 mol/L at pH 7.0 . TETA reacts in a stoichiometric ratio 1:1 with copper and is also able to complex with iron and zinc in vivo. TETA is considered a potential chemotherapeutic agent as it could be a telomerase inhibitor because it is a ligand for G-quadruplex, and stabilizes both intra- and intermolecular G-quadruplexes. It may mediate a selective inhibitory effect or cytotoxicity on tumor growth. Chelating excess copper may affect copper-induced angiogenesis. Other mechanisms of action of TETA for alternative therapeutic implications include improved antioxidant defense against oxidative stress, pro-apoptosis, and reduced inflammation.

Additional Data Available
Adverse Effects

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It is poorly absorbed from the gastrointestinal tract with a bioavailability of 8 to 30% and and what is absorbed is metabolized and inactivated. 5% to 18% that is systemically absorbed in humans is reported to be extensively metabolized 2. The time to reach peak concentration (Tmax) for humans occur between 0.8 to 4 hours 4.

Volume of distribution

It is widely distributed in tissues with relatively high concentrations measured in liver, heart, and kidney. A recent study reported that the central and peripheral volumes of distribution were 393 L and 252 L, respectively 4.

Protein binding
Not Available

It is mainly metabolized via acetylation, and two major acetylated metabolites exist in human serum and urine. TETA is readily acetylated into N1-acetyltriethylenetetramine (MAT) and N1,N10-diacetyltriethylenetetramine (DAT). MAT is still capable of binding divalent Cu, Fe, and Zn but to a much lesser extent compared to the unchanged drug. To date no enzyme has been definitely identified as responsible for TETA acetylation but spermidine/spermine acetyltransferase-1 (SSAT-1) is a potential candidate responsible for acetylation of TETA because of the close chemical resemblance between its natural substrate spermidine and TETA. TETA is also shown to be a substrate for human thialysine acetyltransferase (SSAT2) in vitro.

Route of elimination

The unchanged drug and two acetylated metabolites, N1-acetyltriethylenetetramine (MAT) and N1,N10-diacetyltriethylenetetramine (DAT), are mainly excreted in the urine. About 1% of the administered trientine and about 8% of the biotransformed trientine metabolite, acetyltrien, ultimately appear in the urine. The amounts of urinary copper, zinc and iron increase in parallel with the amount of trientine excreted in the urine 7. Unchanged drug is also excreted in feces after oral administration.

Half life

The plasma elimination half life of TETA in healthy volunteers and Wilson's disease patients ranges from 1.3 to 4 hours. The metabolites are expected to be longer than the parent drug.

Not Available

Neurological worsening may be associated with TETA therapy. Trientine also chelates iron, and co-administration of trientine and iron should be avoided because the complex with iron is toxic. A reversible sideroblastic anemia may be a consequence of overtreatment and resultant copper deficiency. Lupus-like reactions have also been reported 7. The oral LD50 value in rats is rat, mouse, rabbit is 2500mg/kg, 1600mg/kg, and 5500mg/kg, respectively.

Affected organisms
  • Humans and other mammals
Not Available
Pharmacogenomic Effects/ADRs
Not Available


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.
AbacavirAbacavir may decrease the excretion rate of Triethylenetetramine which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Triethylenetetramine which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Triethylenetetramine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Triethylenetetramine which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Triethylenetetramine which could result in a higher serum level.
AcetazolamideThe excretion of Triethylenetetramine can be increased when combined with Acetazolamide.
Acetylcysteine zincThe serum concentration of Acetylcysteine zinc can be decreased when it is combined with Triethylenetetramine.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Triethylenetetramine which could result in a higher serum level.
AclidiniumTriethylenetetramine may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineTriethylenetetramine may decrease the excretion rate of Acrivastine which could result in a higher serum level.
Additional Data Available
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Food Interactions
Not Available


General References
  1. Cho HY, Blum RA, Sunderland T, Cooper GJ, Jusko WJ: Pharmacokinetic and pharmacodynamic modeling of a copper-selective chelator (TETA) in healthy adults. J Clin Pharmacol. 2009 Aug;49(8):916-28. doi: 10.1177/0091270009337939. [PubMed:19602718]
  2. Lu J, Poppitt SD, Othman AA, Sunderland T, Ruggiero K, Willett MS, Diamond LE, Garcia WD, Roesch BG, Cooper GJ: Pharmacokinetics, pharmacodynamics, and metabolism of triethylenetetramine in healthy human participants: an open-label trial. J Clin Pharmacol. 2010 Jun;50(6):647-58. doi: 10.1177/0091270009349379. Epub 2010 Feb 9. [PubMed:20145262]
  3. Lu J, Chan YK, Gamble GD, Poppitt SD, Othman AA, Cooper GJ: Triethylenetetramine and metabolites: levels in relation to copper and zinc excretion in urine of healthy volunteers and type 2 diabetic patients. Drug Metab Dispos. 2007 Feb;35(2):221-7. Epub 2006 Nov 15. [PubMed:17108057]
  4. Lu J: Triethylenetetramine pharmacology and its clinical applications. Mol Cancer Ther. 2010 Sep;9(9):2458-67. doi: 10.1158/1535-7163.MCT-10-0523. Epub 2010 Jul 26. [PubMed:20660601]
  5. Cooper GJ: Therapeutic potential of copper chelation with triethylenetetramine in managing diabetes mellitus and Alzheimer's disease. Drugs. 2011 Jul 9;71(10):1281-320. doi: 10.2165/11591370-000000000-00000. [PubMed:21770477]
  6. Lu J, Gong D, Choong SY, Xu H, Chan YK, Chen X, Fitzpatrick S, Glyn-Jones S, Zhang S, Nakamura T, Ruggiero K, Obolonkin V, Poppitt SD, Phillips AR, Cooper GJ: Copper(II)-selective chelation improves function and antioxidant defences in cardiovascular tissues of rats as a model of diabetes: comparisons between triethylenetetramine and three less copper-selective transition-metal-targeted treatments. Diabetologia. 2010 Jun;53(6):1217-26. doi: 10.1007/s00125-010-1698-8. Epub 2010 Mar 11. [PubMed:20221822]
  7. Authors unspecified: EASL Clinical Practice Guidelines: Wilson's disease. J Hepatol. 2012 Mar;56(3):671-85. doi: 10.1016/j.jhep.2011.11.007. [PubMed:22340672]
External Links
KEGG Compound
PubChem Compound
PubChem Substance
PDBe Ligand
ATC Codes
A16AX12 — Trientine
PDB Entries
Download (48.7 KB)

Clinical Trials

Clinical Trials
1CompletedTreatmentAdvanced Cancers1
1CompletedTreatmentWilson's Disease1
2WithdrawnPreventionMacular Edema Following Cataract Surgery1
3CompletedTreatmentWilson's Disease1
4Active Not RecruitingTreatmentWilson's Disease1
Not AvailableCompletedTreatmentWilson's Disease1
Not AvailableNot Yet RecruitingNot AvailableTrientine Treatment for Wilson's Disease1
Not AvailableTerminatedNot AvailableDiabetic Retinopathy (DR)1


Not Available
Not Available
Dosage forms
CapsuleOral250 mg/1
Capsule, gelatin coatedOral250 mg/1
Not Available
Not Available


Experimental Properties
melting point (°C)12MSDS
boiling point (°C)266MSDS
water solubilitySolubleMSDS
Predicted Properties
Water Solubility27.5 mg/mLALOGPS
pKa (Strongest Basic)9.77ChemAxon
Physiological Charge3ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area76.1 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity43.32 m3·mol-1ChemAxon
Polarizability18.04 Å3ChemAxon
Number of Rings0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available


Mass Spec (NIST)
Not Available
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - EI-BGC-MSsplash10-0006-9000000000-dc59b9e5ca78bd735bee
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0002-0900000000-a71c042b9b4739000226
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000i-9200000000-066d71fec24b87eb78fd
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0083-9000000000-30cc8480e8680b6fc470
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9000000000-3467a5c3550b900f122e
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9000000000-c5b8a993b94560436a51


This compound belongs to the class of organic compounds known as dialkylamines. These are organic compounds containing a dialkylamine group, characterized by two alkyl groups bonded to the amino nitrogen.
Organic compounds
Super Class
Organic nitrogen compounds
Organonitrogen compounds
Sub Class
Direct Parent
Alternative Parents
Organopnictogen compounds / Monoalkylamines / Hydrocarbon derivatives
Secondary aliphatic amine / Organopnictogen compound / Hydrocarbon derivative / Primary amine / Primary aliphatic amine / Aliphatic acyclic compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
tetraamine, polyazaalkane (CHEBI:39501)


Bos taurus
Pharmacological action
General Function
Laminin binding
Specific Function
Cell surface proteoglycan that bears heparan sulfate. Binds, via the heparan sulfate side chains, alpha-4 (V) collagen and participates in Schwann cell myelination (By similarity). May act as a cat...
Gene Name
Uniprot ID
Uniprot Name
Molecular Weight
61006.81 Da
  1. Belting M, Mani K, Jonsson M, Cheng F, Sandgren S, Jonsson S, Ding K, Delcros JG, Fransson LA: Glypican-1 is a vehicle for polyamine uptake in mammalian cells: a pivital role for nitrosothiol-derived nitric oxide. J Biol Chem. 2003 Nov 21;278(47):47181-9. Epub 2003 Sep 11. [PubMed:12972423]

Drug created on September 14, 2010 10:21 / Updated on March 01, 2020 23:29

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