Troglitazone
Encyclopedia
Troglitazone is an anti-diabetic and antiinflammatory drug, and a member of the drug
class of the thiazolidinedione
s. It was developed by Daiichi Sankyo Co.
(Japan). In the United States, it was introduced and manufactured by Parke-Davis
in the late 1990s, but turned out to be associated with an idiosyncratic reaction
leading to drug-induced hepatitis
. One FDA medical officer evaluating troglitazone, John Gueriguian, did not recommend its approval due to potential high liver toxicity, but a full panel of experts approved it in January 1997. Once the prevalence of adverse liver effects became known, troglitazone was withdrawn from the British
market in December 1997, from the United States
market in 2000, and from the Japan
market soon afterwards.
s (pioglitazone
and rosiglitazone
), works by activating peroxisome proliferator-activated receptor
s (PPARs).
Troglitazone is a ligand to both PPARα and – more strongly – PPARγ. Troglitazone also contains an α-tocopheroyl moiety, potentially giving it vitamin E
-like activity in addition to its PPAR activation. It has been shown to reduce inflammation
: troglitazone use was associated with a decrease of nuclear factor kappa-B (NF-κB) and a concomitant increase in its inhibitor (IκB). NFκB is an important cellular transcription regulator for the immune response.
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
class of the thiazolidinedione
Thiazolidinedione
The thiazolidinediones , also known as glitazones, are a class of medications used in the treatment of diabetes mellitus type 2. They were introduced in the late 1990s.- Mechanism of action :...
s. It was developed by Daiichi Sankyo Co.
Daiichi Sankyo Co.
is a global pharmaceutical company and the second largest pharmaceutical company in Japan. It achieved JPY 970 billion in revenue in 2010 and is currently ranked number 17 in world sales. Its headquarter is based in Tokyo. The company also owns the American biotechnology company Plexxikon, the...
(Japan). In the United States, it was introduced and manufactured by Parke-Davis
Parke-Davis
Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although no longer an independent corporation, it was once America's oldest and largest drug maker, and played an important role in medical history.- History :...
in the late 1990s, but turned out to be associated with an idiosyncratic reaction
Idiosyncratic drug reaction
Idiosyncratic drug reactions, also known as type B reactions, are drug reactions that occur rarely and unpredictably amongst the population. This is not to be mistaken with idiopathic, which implies that the cause is not known...
leading to drug-induced hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
. One FDA medical officer evaluating troglitazone, John Gueriguian, did not recommend its approval due to potential high liver toxicity, but a full panel of experts approved it in January 1997. Once the prevalence of adverse liver effects became known, troglitazone was withdrawn from the British
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
market in December 1997, from the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
market in 2000, and from the Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
market soon afterwards.
Mode of action
Troglitazone, like the other thiazolidinedioneThiazolidinedione
The thiazolidinediones , also known as glitazones, are a class of medications used in the treatment of diabetes mellitus type 2. They were introduced in the late 1990s.- Mechanism of action :...
s (pioglitazone
Pioglitazone
Pioglitazone is a prescription drug of the class thiazolidinedione with hypoglycemic action.Pioglitazone is marketed as trademarks Actos in the USA, Canada, the UK and Germany, Glustin in Europe,"Glizone" and "Pioz" in India by Zydus CND and USV respectively and Zactos in Mexico by Takeda...
and rosiglitazone
Rosiglitazone
Rosiglitazone is an antidiabetic drug in the thiazolidinedione class of drugs. It works as an insulin sensitizer, by binding to the PPAR receptors in fat cells and making the cells more responsive to insulin...
), works by activating peroxisome proliferator-activated receptor
Peroxisome proliferator-activated receptor
In the field of molecular biology, the peroxisome proliferator-activated receptors are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes...
s (PPARs).
Troglitazone is a ligand to both PPARα and – more strongly – PPARγ. Troglitazone also contains an α-tocopheroyl moiety, potentially giving it vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...
-like activity in addition to its PPAR activation. It has been shown to reduce inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
: troglitazone use was associated with a decrease of nuclear factor kappa-B (NF-κB) and a concomitant increase in its inhibitor (IκB). NFκB is an important cellular transcription regulator for the immune response.
External links
- Diabetes Monitor article on troglitazone
- RxList article on troglitazone