Triparanol

Triparanol
Clinical data
Other namesMetasqualene
ATC code
  • None
Identifiers
IUPAC name
  • 2-(4-Chlorophenyl)-1-[4-[2-(diethylamino)ethoxy]phenyl]-1-(4-methylphenyl)ethanol
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard100.001.014
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Chemical and physical data
FormulaC27H32ClNO2
Molar mass438.01 g·mol−1
3D model (JSmol)
SMILES
  • CCN(CC)CCOC1=CC=C(C=C1)C(CC2=CC=C(C=C2)Cl)(C3=CC=C(C=C3)C)O
InChI
  • InChI=1S/C27H32ClNO2/c1-4-29(5-2)18-19-31-26-16-12-24(13-17-26)27(30,23-10-6-21(3)7-11-23)20-22-8-14-25(28)15-9-22/h6-17,30H,4-5,18-20H2,1-3H3
  • Key:SYHDSBBKRLVLFF-UHFFFAOYSA-N

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code name of triparanol, MER/29, became so well known that it became the registered trade name of the drug.[5] It was withdrawn in 1962 due to severe adverse effects such as nausea and vomiting, vision loss due to irreversible cataracts, alopecia, skin disorders (e.g., dryness, itching,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

References

  1. ↑ Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 1252–. ISBN 978-1-4757-2085-3.
  2. 1 2 3 4 5 6 Ravina E (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. 1 2 3 4 5 6 7 Li JJ (3 April 2009). Triumph of the Heart: The Story of Statins. Oxford University Press, USA. pp. 33–. ISBN 978-0-19-532357-3.
  4. ↑ Vance DE, Vance JE (200). Biochemistry of Lipids, Lipoproteins, and Membranes. Elsevier. pp. 172–174. ISBN 978-0-444-51138-6.
  5. ↑ Miller LC (July 1961). "Doctors, drugs, and names". JAMA. 177 (1): 27–33. 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).
  6. ↑ Burtis CA, Ashwood ER, Bruns DE (14 October 2012). Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Elsevier Health Sciences. pp. 733–. ISBN 978-1-4557-5942-2.
  7. 1 2 Grant WM, Schuman JS (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. ↑ Manni A (15 January 1999). Endocrinology of Breast Cancer. Springer Science & Business Media. pp. 286–. ISBN 978-1-59259-699-7.
  9. ↑ Aronson JK (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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