Triparanol

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cholesterol-lowering drug.[1][2] It was patented in 1959 and introduced in the United States in 1960.[3][4] It was withdrawn in 1962 due to severe adverse effects such as nausea and vomiting, vision loss due to irreversible cataracts, alopecia, skin disorders (e.g., dryness, itching,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.[3][2]

Triparanol
Clinical data
Other namesMetasqualene
ATC code
  • None
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard100.001.014
Chemical and physical data
FormulaC27H32ClNO2
Molar mass438.01 g·mol−1
3D model (JSmol)

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.[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 significantly lower cholesterol levels without resulting in accumulation of intermediates like desmosterol.[2] 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.[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] and 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".[3]

See also

References
  1. 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.
  2. 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.
  3. 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.
  4. Dennis E. Vance; Jean E. Vance (2002). Biochemistry of Lipids, Lipoproteins, and Membranes. Elsevier. pp. 172–174. ISBN 978-0-444-51138-6.
  5. 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 978-1-4557-5942-2.
  6. Miller, Lloyd C. (1961). "Doctors, Drugs, and Names". JAMA. 177 (1): 27. doi:10.1001/jama.1961.73040270014004b. ISSN 0098-7484. 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).
  7. 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.
  8. Andrea Manni (15 January 1999). Endocrinology of Breast Cancer. Springer Science & Business Media. pp. 286–. ISBN 978-1-59259-699-7.
  9. Aronson, Jeffrey K. (21 February 2009). Meyler's Side Effects of Endocrine and Metabolic Drugs. Elsevier. pp. 163–. ISBN 978-0-08-093292-7.
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