Triparanol
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| Identifiers | |
|---|---|
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| Synonyms | Metasqualene |
| CAS Number | 78-41-1 |
| PubChem (CID) | 6536 |
| ChemSpider | 6288 |
| Chemical and physical data | |
| Formula | C27H32ClNO2 |
| Molar mass | 438.00148 g/mol |
| 3D model (Jmol) | Interactive image |
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Triparanol (INN, BAN) (brand and developmental code names MER/29, as well as many other brand names), patented in 1959 and introduced in the United States in 1960,[1][2] was the first synthetic cholesterol-lowering drug.[3][4] It was withdrawn in 1962 due to severe adverse effects such as nausea and vomiting, vision loss due to irreversible cataracts, alopecia, skin disorders (e.g., dryness, itching, peeling, and "fish-scale" texture), and accelerated atherosclerosis and is now considered to be obsolete.[1][4] The drug acts by inhibiting 24-dehydrocholesterol reductase, which catalyzes the final step of cholesterol biosynthesis, the conversion of desmosterol into cholesterol.[5] This results in tissue accumulation of desmosterol, which in turn is responsible for the side effects of triparanol.[4] Unlike statins, triparanol does not inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis,[4] and in contrast to triparanol, statins can significantly lower cholesterol levels without resulting in accumulation of intermediates like desmosterol.[4] The developmental code name of triparanol, MER/29, became so well-known that it became the registered trade name of the drug.[6]
Estrogen is known to lower cholesterol levels, but produces side effects like gynecomastia and decreased libido in men.[1] It was hoped that a drug could be developed that lacked overt estrogenic effects but still lowered cholesterol levels.[1] Triparanol was derived from chlorotrianisene (TACE), a non-steroidal estrogen,[1][7] and the non-steroidal antiestrogen ethamoxytriphetol (MER-25) is a derivative of triparanol.[8] The selective estrogen receptor modulator clomifene is also structurally related to triparanol.[7][9] The developers of triparanol jokingly referred to it as a "non-estrogenic estrogen".[1]
See also
References
- 1 2 3 4 5 6 Jie Jack Li (3 April 2009). Triumph of the Heart: The Story of Statins. Oxford University Press, USA. pp. 33–. ISBN 978-0-19-532357-3.
- ↑ Dennis E. Vance; Jean E. Vance (2002). Biochemistry of Lipids, Lipoproteins, and Membranes. Elsevier. pp. 172–174. ISBN 978-0-444-51138-6.
- ↑ J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 1252–. ISBN 978-1-4757-2085-3.
- 1 2 3 4 5 Enrique Ravina (11 January 2011). The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs. John Wiley & Sons. pp. 178–. ISBN 978-3-527-32669-3.
- ↑ Carl A. Burtis; Edward R. Ashwood; David E. Bruns (14 October 2012). Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Elsevier Health Sciences. pp. 733–. ISBN 1-4557-5942-2.
- ↑ Miller, Lloyd C. (1961). "Doctors, Drugs, and Names". JAMA. 177 (1): 27. doi:10.1001/jama.1961.73040270014004b. ISSN 0098-7484.
Recently, another laboratory code number, MER29, became so well known that it was adopted as the registered trademark for the anticholesterolemic drug concerned (triparanol).
- 1 2 W. Morton Grant; Joel S. Schuman (1 January 1993). TOXICOLOGY OF THE EYE: Effects on the Eyes and Visual System from Chemicals, Drugs, Metals and Minerals, Plants, Toxins and Venoms; also Systemic Side Effects from Eye Medications (4th Ed.). Charles C Thomas Publisher. pp. 384–. ISBN 978-0-398-08215-4.
- ↑ Andrea Manni (15 January 1999). Endocrinology of Breast Cancer. Springer Science & Business Media. pp. 286–. ISBN 978-1-59259-699-7.
- ↑ Jeffrey K. Aronson (21 February 2009). Meyler's Side Effects of Endocrine and Metabolic Drugs. Elsevier. pp. 163–. ISBN 978-0-08-093292-7.