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| Clinical data | |
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| Trade names | MER/29 |
| Other names | Metasqualene |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.001.014 |
| Chemical and physical data | |
| Formula | C27H32ClNO2 |
| Molar mass | 438.01 g·mol−1 |
| 3D model (JSmol) | |
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Triparanol (INNTooltip International Nonproprietary Name,BANTooltip British Approved Name; brand name and development codeMER/29, as well as many other brand names) was the firstsyntheticcholesterol-loweringdrug.[1][2] It was patented in 1959 and introduced in theUnited 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 waswithdrawn in 1962 due to severeadverse effects such asnausea andvomiting,vision loss due to irreversiblecataracts,alopecia,skin disorders (e.g.,dryness,itching,peeling, and "fish-scale" texture), and acceleratedatherosclerosis.[3][2] It is now considered to be obsolete.[3][2]
The drug acts by inhibiting24-dehydrocholesterol reductase, which catalyzes the final step of cholesterolbiosynthesis, the conversion ofdesmosterol 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] Unlikestatins, triparanol does not inhibitHMG-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 producesside effects likegynecomastia and decreasedlibido 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 atriphenylethanol and was derived fromchlorotrianisene (TACE), anonsteroidaltriphenylethylene estrogen.[3][7] The nonsteroidal triphenylethanolantiestrogenethamoxytriphetol (MER-25) is a derivative of triparanol.[8] Theselective estrogen receptor modulatorclomifene 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]
Recently, another laboratory code number, MER29, became so well known that it was adopted as the registered trademark for the anticholesterolemic drug concerned (triparanol).