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 accommo ...

) when used medically, is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

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 betwee ...

H₂NHCH₂CH₂NH₂sub>2. The pure freebase is a colorless oily liquid, but, like many

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...

s, older samples assume a yellowish color due to impurities resulting from air-oxidation. It is soluble in polar solvents. The branched

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...

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. Abbrev ...

and

piperazine Piperazine () is an organic compound that consists of a six-membered ring containing two nitrogen atoms at opposite positions in the ring. Piperazine exists as small alkaline deliquescent crystals with a saline taste. The piperazines are a broad ...

derivatives may also be present in commercial samples of TETA. The hydrochloride salts are used medically as a treatment for copper toxicity.

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 cured end products of epoxy resins. Epoxy resins, also known as polyepoxides, are a class of reactive prepolymers and polymers which contain epoxide groups. The epoxide functional group is also coll ...

curing.

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 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 ligands are ...

that is used to bind and remove

copper Copper is a chemical element with the symbol Cu (from la, cuprum) 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 pinkis ...

in the body to treat

Wilson's disease Wilson's disease is a genetic disorder in which excess copper builds up in the body. Symptoms are typically related to the brain and liver. Liver-related symptoms include vomiting, weakness, fluid build up in the abdomen, swelling of the legs, ...

, 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 © 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 © 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. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

, especially when starting treatment,

skin rash A rash is a change of the human skin which 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, cr ...

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

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

colitis Colitis is swelling or inflammation of the large intestine ( colon). Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases. In a medical context, the label ''colitis'' (without qualification) ...

(inflammation in the large bowel causing pain and

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

Society and culture

Controversies

In the United States,

Valeant Pharmaceuticals International Bausch Health Companies Inc. (formerly Valeant Pharmaceuticals International, Inc.) is a Canadian multinational specialty pharmaceutical company based in Laval, Quebec, Canada. It develops, manufactures and markets pharmaceutical products and ...

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'' (''the Times'', ''NYT'', or the Gray Lady) is a daily newspaper based in New York City with a worldwide readership reported in 2020 to comprise a declining 840,000 paid print subscribers, and a growing 6 million paid ...

'' 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 company with headquarters in Tel Aviv, Israel. It specializes primarily in generic drugs, but other business interests include ...

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 an organic chemical compound with the formula or . The molecule is bifunctional, containing both a primary amine and a primary alcohol. Ethanolamine is a colorless, viscous liquid wit ...

ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous was ...

mixtures over an oxide

catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

. 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 (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 electr ...

coordination chemistry A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Many ...

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

References

External links

* * * {{Portal bar , Medicine Ethyleneamines Chelating agents Orphan drugs Tetradentate ligands Secondary amines X