Wikipedia - Troglitazone
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| Systematic (IUPAC) name | |
| (RS)-5-(4-[(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)methoxy]benzyl)thiazolidine-2,4-dione | |
| Identifiers | |
| CAS number | 97322-87-7 |
| ATC code | A10BG01 |
| PubChem | CID 5591 |
| DrugBank | APRD00488 |
| Chemical data | |
| Formula | C24H27NO5S |
| Mol. mass | 441.541 g/mol |
| Pharmacokinetic data | |
| Half-life | 16-34 hours |
| Therapeutic considerations | |
| Pregnancy cat. | ? |
| Legal status | |
Troglitazone (Rezulin, Resulin or Romozin) is an anti-diabetic and antiinflammatory drug, and a member of the drug class of the thiazolidinediones. 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,[1] but a full panel of experts approved it in January 1997.[2] Subsequently, once the prevalence of adverse liver effects became known, troglitazone was withdrawn from the United Kingdom market in December 1997, from the USA market in 2000, and from the Japan market soon afterwards.
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[edit] Mode of action
Troglitazone, like the other thiazolidinediones (pioglitazone and rosiglitazone), works by activating PPARs (peroxisome proliferator-activated receptors).
Troglitazone is a ligand to both PPARa and - more strongly - PPAR?. Troglitazone also contains an a-tocopheroyl moiety, potentially giving it vitamin E-like activity in addition to its PPAR activation. It has been shown to reduce inflammation:[3] troglitazone use was associated with a decrease of nuclear factor kappa-B (NF-?B) and a concomitant increase in its inhibitor (I?B). NF?B is an important cellular transcription regulator for the immune response.
[edit] Chemistry
Yoshioka, Takao; Fujita, Takashi; Kanai, Tsutomu; Aizawa, Yuichi; Kurumada, Tomoyuki; Hasegawa, Kazuo; Horikoshi, Hiroyoshi (1989). "Studies on hindered phenols and analogs. 1. Hypolipidemic and hypoglycemic agents with ability to inhibit lipid peroxidation". Journal of Medicinal Chemistry 32: 421. doi:10.1021/jm00122a022.
[edit] References
- ^ Retired Drugs: Failed Blockbusters, Homicidal Tampering, Fatal Oversights, wired.com
- ^ Cohen, J. S. (2006). "Risks of troglitazone apparent before approval in USA". Diabetologia 49 (6): 1454. doi:10.1007/s00125-006-0245-0. PMID 16601971.
- ^ Aljada A, Garg R, Ghanim H, et al. (2001). "Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of troglitazone in obese patients with type 2 diabetes: evidence of an antiinflammatory action?". J. Clin. Endocrinol. Metab. 86 (7): 3250–6. doi:10.1210/jc.86.7.3250. PMID 11443197.
[edit] External links
- Diabetes Monitor article on troglitazone
- RxList article on troglitazone
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This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Troglitazone".
