Probucol, sold under the trade name Lorelco among others, is an anti- hyperlipidemic

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 ...

initially developed for the treatment of

coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves Ischemia, the reduction of blood flow to the myocardium, heart muscle due to build-up o ...

. Clinical development was discontinued after it was found that the drug may have the undesired effect of lowering HDL in patients with a previous history of heart disease. It may also cause QT interval prolongation. Probucol was initially developed in the 1970s by a chemical company to maximize airplane tire longevity.

Mechanism of action

Probucol lowers the level of

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell membr ...

in the bloodstream by increasing the rate of LDL

catabolism Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipids ...

. Additionally, probucol may inhibit

cholesterol synthesis The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopenten ...

and delay cholesterol absorption. Probucol is a powerful

antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricants ...

which inhibits the oxidation of cholesterol in LDLs; this slows the formation of

foam cell Foam cells, also called lipid-laden macrophages, are a type of cell that contain cholesterol. These can form a plaque that can lead to atherosclerosis and trigger heart attacks and stroke. Foam cells are fat-laden cells with a M2 macrophage-like ...

s, which form

atherosclerotic 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 no s ...

plaques. After promising test results in mouse models, Probucol is under study at Weston Brain Institute of McGill University as a possible aid in delaying the onset of Alzheimer's disease. Probucol has also been shown to inhibit

ABCA1 ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub-family ABCA), also known as the ''cholesterol efflux regulatory protein'' (CERP) is a protein which in humans is encoded by the ''ABCA1'' gene. This transporter is a major ...

-dependent cholesterol transport, which may contribute to its known effect of lowering HDL.

References

{{Lipid modifying agents Antioxidants Phenols Thioethers Tert-butyl compounds