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

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

-lowering

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

. It was patented in 1959 and introduced in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

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 It was withdrawn in 1962 due to severe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 medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term compli ...

s such as

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

and

vomiting Vomiting (also known as emesis, puking and throwing up) is the 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, gastroenteritis, pre ...

vision loss Visual or vision impairment (VI or VIP) is the partial or total inability of visual perception. In the absence of treatment such as corrective eyewear, assistive devices, and medical treatment, visual impairment may cause the individual difficul ...

due to irreversible

cataracts A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision of the eye. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colours, blurry or double vision, halos around ligh ...

alopecia Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarring ...

skin disorder A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, Nail (anatomy), nails, and related muscle and glands. The major funct ...

s (e.g., dryness,

itching An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...

, peeling, and "fish-scale" texture), and accelerated

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...

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

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

, the conversion of desmosterol 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 (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...

s, triparanol does not inhibit

HMG-CoA reductase HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, official symbol HMGCR) is the rate-limiting enzyme (NADH-dependent, ; NADPH-dependent, ) of the mevalonate pathway, the metabolic pathway that produces cholesterol and other ...

, 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 (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

is known to lower cholesterol levels, but produces

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s like

gynecomastia Gynecomastia (also spelled gynaecomastia) is the non-cancerous enlargement of one or both breasts in men due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (10 Novemb ...

and decreased

libido In psychology, libido (; ) is psychic drive or energy, usually conceived of as sexual in nature, but sometimes conceived of as including other forms of desire. The term ''libido'' was originally developed by Sigmund Freud, the pioneering origin ...

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 and was derived from

chlorotrianisene Chlorotrianisene (CTA), also known as tri-''p''-anisylchloroethylene (TACE) and sold under the brand name Tace among others, is a nonsteroidal estrogen related to diethylstilbestrol (DES) which was previously used in the treatment of menopausal ...

(TACE), a

nonsteroidal A nonsteroidal compound is a drug that is not a steroid nor a steroid derivative. Nonsteroidal anti-inflammatory drugs (NSAIDs) are distinguished from corticosteroids as a class of anti-inflammatory agents. List of nonsteroidal steroid receptor mo ...

triphenylethylene Triphenylethylene (TPE) is the organic compound with the formula . It is a colorless solid. Synthesis and reactions The compound is prepared in two steps from benzophenone via the intermediacy of 1,2,2-triphenylethanol. Triphenylethylene reacts ...

estrogen. The nonsteroidal triphenylethanol

antiestrogen Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or inh ...

ethamoxytriphetol Ethamoxytriphetol (developmental code name MER-25) is a synthetic nonsteroidal antiestrogen that was studied clinically in the late 1950s and early 1960s but was never marketed. MER-25 was first reported in 1958, and was the first antiestrogen t ...

(MER-25) is a derivative of triparanol. The

selective estrogen receptor modulator Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonists/antagonists (ERAAs), are a class of drugs that act on estrogen receptors (ERs). Compared to pure ER agonists–antagonists (e.g., full agonists and silent ...

clomifene Clomifene, also known as clomiphene, is a medication used to treat infertility in women who do not ovulate, including those with polycystic ovary syndrome. It is taken by mouth. Common side effects include pelvic pain and hot flashes. Oth ...

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 4-Chlorophenyl compounds Phenol ethers Withdrawn drugs Ethanolamines

See also

References