Triethylenetetramine (TETA and trien), also known as trientine (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...

) when used medically, is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

with the

formula In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwe ...

H₂NHCH₂CH₂NH₂sub>2. The pure

free base In chemistry, a free base (freebase, free-base) is a term for the neutral form of an amine or other Lewis base. The term is used in the pharmaceutical industry in contrast to salt-based formulations like hydrochlorides. The amine is often an ...

is a colorless oily liquid, but, like many

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

s, older samples assume a yellowish color due to impurities resulting from air

oxidation Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...

. It is soluble in polar solvents. The branched

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...

tris(2-aminoethyl)amine Tris(2-aminoethyl)amine is the organic compound with the chemical formula, formula N(CH2CH2NH2)3. This colourless liquid is soluble in water and is highly basic, consisting of a tertiary amine center and three pendant primary amine groups. Tris(2- ...

and

piperazine Piperazine () is an organic compound with the formula . In term of its structure, it can be described as cyclohexane with the 1- and 4-CH2 groups replaced by NH. Piperazine exists as deliquescent solid with a saline taste. Piperazine is freely sol ...

derivatives may also be present in commercial samples of TETA. The

hydrochloride In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternati ...

salts are used medically as a treatment for

copper toxicity Copper toxicity (or Copperiedus) is a type of metal poisoning caused by an excess of copper in the body. Copperiedus could occur from consuming excess copper salts, but most commonly it is the result of the genetic condition Wilson's disease a ...

Uses

Epoxy uses

The reactivity and uses of TETA are similar to those for the related polyamines

ethylenediamine Ethylenediamine (abbreviated as en when a ligand) is the organic compound with the formula C2H4(NH2)2. This colorless liquid with an ammonia-like odor is a basic amine. It is a widely used building block in chemical synthesis, with approximately ...

and

diethylenetriamine Diethylenetriamine (abbreviated and also known as 2,2’-Iminodi(ethylamine)) is an organic compound with the formula HN(CH2CH2NH2)2. This colourless hygroscopic liquid is soluble in water and polar organic solvents, but not simple hydrocarbons. ...

. It is primarily used as a crosslinker ("hardener") in

epoxy Epoxy is the family of basic components or Curing (chemistry), cured end products of epoxy Resin, resins. Epoxy resins, also known as polyepoxides, are a class of reactive prepolymers and polymers which contain epoxide groups. The epoxide fun ...

curing. TETA, like other aliphatic amines, react quicker and at lower temperatures than aromatic amines due to less negative

steric effects Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is generally a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape (conformational isomerism, co ...

since the linear nature of the molecule provides it the ability to rotate and twist.

Medical uses

The hydrochloride salt of TETA, referred to as ''trientine hydrochloride'', is a

chelating agent Chelation () is a type of bonding of ions and their molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These l ...

that is used to bind and remove

copper Copper is a chemical element; it has symbol Cu (from Latin ) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkish-orang ...

in the body to treat

Wilson's disease Wilson's disease (also called hepatolenticular degeneration) is a genetic disorder characterized by the excess build-up of copper in the body. Symptoms are typically related to the brain and liver. Liver-related symptoms include vomiting, wea ...

, particularly in those who are intolerant to

penicillamine Penicillamine, sold under the brand name of Cuprimine among others, is a medication primarily used for the treatment of Wilson's disease. It is also used for people with kidney stones who have high urine cystine levels, rheumatoid arthritis, ...

. Some recommend trientine as first-line treatment, but experience with penicillamine is more extensive. Trientine hydrochloride (brand name Syprine) was approved for medical use in the United States in November 1985. Trientine tetrahydrochloride (brand name Cuprior) was approved for medical use in the European Union in September 2017. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. It is indicated for the treatment of Wilson's disease in adults, adolescents and children five years of age or older who are intolerant to D-penicillamine therapy. Trientine dihydrochloride (brand name Cufence) was approved for medical use in the European Union in July 2019. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. It is indicated for the treatment of Wilson's disease in adults, adolescents and children five years of age or older who are intolerant to D-penicillamine therapy. The most common side effects include

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

, especially when starting treatment,

skin rash A rash is a change of the skin that affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked ...

duodenitis Duodenitis is inflammation of the duodenum. It may persist acutely or chronically. Signs and symptoms Known symptoms of duodenitis include: * Abdominal pain * nausea * vomiting * discomfort in stomach Causes Known causes of duodenitis include ...

(inflammation of the duodenum, the part of the gut leading out of the stomach), and severe

colitis Colitis is swelling or inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and ...

(inflammation in the large bowel causing pain and

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

Society and culture

Controversies

In the United States,

Valeant Pharmaceuticals International Bausch Health Companies Inc. is a global, diversified American-Canadian pharmaceutical company. Its global corporate headquarters are located in Laval, Quebec, Canada, and its U.S. headquarters are in Bridgewater, New Jersey. It develops, manufa ...

raised the price of its Syprine brand of TETA from $625 to $21,267 for 100 pills over five years. ''

The New York Times ''The New York Times'' (''NYT'') is an American daily newspaper based in New York City. ''The New York Times'' covers domestic, national, and international news, and publishes opinion pieces, investigative reports, and reviews. As one of ...

'' said that this "egregious" price increase caused public outrage.

Teva Pharmaceuticals Teva Pharmaceutical Industries Ltd. (also known as Teva Pharmaceuticals) is an Israeli multinational Pharmaceutical industry, pharmaceutical company. Teva specializes primarily in generic drugs, but other business interests include branded-drug ...

developed a generic, which patients and doctors expected to be cheaper, but when it was introduced in February 2018, Teva's price was $18,375 for 100 pills. Aaron Kesselheim, who studies drug pricing at Harvard Medical School, said that drug companies price the product at what they think the market will bear.

Production

TETA is prepared by heating ethylenediamine or

ethanolamine Ethanolamine (2-aminoethanol, monoethanolamine, ETA, or MEA) is a naturally occurring organic chemical compound with the formula or . The molecule is bifunctional, containing both a primary amine and a primary alcohol. Ethanolamine is a colorl ...

ammonia Ammonia is an inorganic chemical compound of nitrogen and hydrogen with the chemical formula, formula . A Binary compounds of hydrogen, stable binary hydride and the simplest pnictogen hydride, ammonia is a colourless gas with a distinctive pu ...

mixtures over an oxide

catalyst Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

. This process gives a variety of amines, especially ethylene amines which are separated by distillation and sublimation.

Coordination chemistry

TETA is a tetradentate

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

coordination chemistry A coordination complex is a chemical compound consisting of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of chemical bond, bound molecules or ions, that are in turn known as ' ...

, where it is referred to as trien. Octahedral complexes of the type M(trien)L₂ can adopt several diastereomeric structures.

References

{{Portal bar , Medicine Aminoethyl compounds Chelating agents Orphan drugs Tetradentate ligands Secondary amines X