Triparanol (, ; brand name and development code MER/29, as well as many other brand names) was the first

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

cholesterol-lowering

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhal ...

. It was patented in 1959 and introduced in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., federal district, five ma ...

in 1960. The developmental code name of triparanol, MER/29, became so well known that it became the registered trade name of the drug. It was withdrawn in 1962 due to severe

adverse effect An adverse effect is an undesired harmful effect resulting from a Pharmaceutical drug, medication or other Surgery#Definitions, intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main ...

s such as

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

and

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...

, vision loss due to irreversible cataracts, alopecia, skin disorders (e.g., dryness, itching, peeling, and "fish-scale" texture), and accelerated

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually ...

. It is now considered to be obsolete. The drug acts by inhibiting 24-dehydrocholesterol reductase, which catalyzes the final step of cholesterol biosynthesis, the conversion of

desmosterol Desmosterol is a molecule similar to cholesterol. Desmosterol is the immediate precursor of cholesterol in the Bloch pathway of cholesterol biosynthesis. 24-dehydrocholesterol reductase catalyses the reduction of desmosterol to cholesterol. It i ...

into cholesterol. Although effective in reducing cholesterol levels, this results in tissue accumulation of desmosterol, which in turn is responsible for the side effects of triparanol. Unlike

statin Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. L ...

s, triparanol does not inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, and in contrast to triparanol, statins can lower cholesterol levels without resulting in accumulation of intermediates like desmosterol.

Estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal a ...

is known to lower cholesterol levels, but produces

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s like gynecomastia and decreased

libido Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act ...

in men. It was hoped that a drug could be developed that lacked overt estrogenic effects but still lowered cholesterol levels. Triparanol is a

triphenylethanol Triphenylethanol, or 1,1,2-triphenylethanol, is an organic compound with a condensed structural formula of , and is related to triphenylethylene, from which it can be prepared by hydration. It is the structural analog of two drugs, the never-m ...

and was derived from chlorotrianisene (TACE), a nonsteroidal triphenylethylene estrogen. The nonsteroidal triphenylethanol antiestrogen ethamoxytriphetol (MER-25) is a derivative of triparanol. The selective estrogen receptor modulator clomifene is also structurally related to triparanol. The developers of triparanol jokingly referred to it as a "non-estrogenic estrogen" due to its lipid-lowering effects without other estrogenic effects.

References

{{Lipid modifying agents 24-Dehydrocholesterol reductase inhibitors Tertiary alcohols Diethylamino compounds Hypolipidemic agents Organochlorides Phenol ethers Withdrawn drugs

See also

References