Triparanol
Pharmaceutical drug
From Wikipedia, the free encyclopedia
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code name of triparanol, MER/29, became so well known that it became the registered trade name of the drug.[5] It was withdrawn in 1962 due to severe adverse effects such as nausea and vomiting, vision loss due to irreversible cataracts, alopecia, skin disorders (e.g., dryness, itching,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]
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| Trade names | MER/29 |
| Other names | Metasqualene |
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| ECHA InfoCard | 100.001.014 |
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| Formula | C27H32ClNO2 |
| Molar mass | 438.01 g·mol−1 |
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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]