Chemistry:Triparanol
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| Trade names | MER/29 |
| Other names | Metasqualene |
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| Formula | C27H32ClNO2 |
| Molar mass | 438.01 g·mol−1 |
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Triparanol (INN, BAN; brand name and development code MER/29, as well as many other brand names) was the first synthetic cholesterol-lowering drug.[1][2] It was patented in 1959 and introduced in the United States in 1960.[3][4] The developmental code name of triparanol, MER/29, became so well known that it became the registered trade name of the drug.[5] It was withdrawn in 1962 due to severe adverse effects such as nausea and vomiting, vision loss due to irreversible cataracts, alopecia, skin disorders (e.g., dryness, itching,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.[3][2] It is now considered to be obsolete.[3][2]
The drug acts by inhibiting 24-dehydrocholesterol reductase, which catalyzes the final step of cholesterol biosynthesis, the conversion of desmosterol into cholesterol.[6] Although effective in reducing cholesterol levels, this results in tissue accumulation of desmosterol, which in turn is responsible for the side effects of triparanol.[2] Unlike statins, triparanol does not inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis,[2] and in contrast to triparanol, statins can lower cholesterol levels without resulting in accumulation of intermediates like desmosterol.[2]
Estrogen is known to lower cholesterol levels, but produces side effects like gynecomastia and decreased libido in men.[3] It was hoped that a drug could be developed that lacked overt estrogenic effects but still lowered cholesterol levels.[3] Triparanol is a triphenylethanol and was derived from chlorotrianisene (TACE), a nonsteroidal triphenylethylene estrogen.[3][7] The nonsteroidal triphenylethanol 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" due to its lipid-lowering effects without other estrogenic effects.[3]
See also
- Azacosterol
- Desmosterolosis
- X-linked ichthyosis
- Clomestrone
- Mytatrienediol
References
- ↑ The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014. pp. 1252–. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA1252.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs. John Wiley & Sons. 11 January 2011. pp. 178–. ISBN 978-3-527-32669-3. https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA178.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Triumph of the Heart: The Story of Statins. Oxford University Press, USA. 3 April 2009. pp. 33–. ISBN 978-0-19-532357-3. https://books.google.com/books?id=-GPl1PA5EgMC&pg=PA33.
- ↑ "Animal Models of Atherosclerosis". Biochemistry of Lipids, Lipoproteins, and Membranes. Elsevier. 200. pp. 172–174. ISBN 978-0-444-51138-6. https://books.google.com/books?id=MQp2AB9QnoMC&pg=PA17.
- ↑ "Doctors, drugs, and names". JAMA 177 (1): 27–33. July 1961. doi:10.1001/jama.1961.73040270014004b. PMID 13770852. "Recently, another laboratory code number, MER29, became so well known that it was adopted as the registered trademark for the anticholesterolemic drug concerned (triparanol).".
- ↑ "Lipids, Lipoproteins, Apoliporoteins, and Other Cardiac Risk Factors". Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Elsevier Health Sciences. 14 October 2012. pp. 733–. ISBN 978-1-4557-5942-2. https://books.google.com/books?id=BBLRUI4aHhkC&pg=PA733.
- ↑ 7.0 7.1 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. 1 January 1993. pp. 384–. ISBN 978-0-398-08215-4. https://books.google.com/books?id=mDLYCQAAQBAJ&pg=PA384.
- ↑ Endocrinology of Breast Cancer. Springer Science & Business Media. 15 January 1999. pp. 286–. ISBN 978-1-59259-699-7. https://books.google.com/books?id=7DSYBwAAQBAJ&pg=PA286.
- ↑ Meyler's Side Effects of Endocrine and Metabolic Drugs. Elsevier. 21 February 2009. pp. 163–. ISBN 978-0-08-093292-7. https://books.google.com/books?id=BWMeSwVwfTkC&pg=PA163.
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