Triparanol

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code name of triparanol, MER/29, became so well known that it became the registered trade name of the drug.^[5] It was withdrawn in 1962 due to severe adverse effects such as nausea and vomiting, vision loss due to irreversible cataracts, alopecia, skin disorders (e.g., dryness,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

Triparanol

Clinical data
Trade names	MER/29
Other names	Metasqualene
ATC code	None
Identifiers
IUPAC name 2-(4-Chlorophenyl)-1-[4-[2-(diethylamino)ethoxy]phenyl]-1-(4-methylphenyl)ethanol
CAS Number	78-41-1
PubChem CID	6536
ChemSpider	6288
UNII	63S8C3RXGS
ChEBI	CHEBI:135714
CompTox Dashboard (EPA)	DTXSID6046507
ECHA InfoCard	100.001.014
Chemical and physical data
Formula	C27H32ClNO2
Molar mass	438.01 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCN(CC)CCOc1ccc(C(O)(Cc2ccc(Cl)cc2)c2ccc(C)cc2)cc1
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

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

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. 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. Li JL (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). "Animal Models of Atherosclerosis". 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). "Lipids, Lipoproteins, Apoliporoteins, and Other Cardiac Risk Factors". Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Elsevier Health Sciences. pp. 733–. ISBN 978-1-4557-5942-2.
7. 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.