Probucol Explained

Verifiedfields:changed
Verifiedrevid:464214831
Iupac Name:4,4'-[Propane-2,2-diylbis(thio)]bis(2,6-di-tert-butylphenol)
Pronounce:
Tradename:Lorelco
Iuphar Ligand:7277
Cas Number:23288-49-5
Atc Prefix:C10
Atc Suffix:AX02
Pubchem:4912
Drugbank:DB01599
Chemspiderid:4743
Unii:P3CTH044XJ
Kegg:D00476
Chebi:8427
Chembl:608
C:31
H:48
O:2
S:2
Smiles:S(c1cc(c(O)c(c1)C(C)(C)C)C(C)(C)C)C(Sc2cc(c(O)c(c2)C(C)(C)C)C(C)(C)C)(C)C
Stdinchi:1S/C31H48O2S2/c1-27(2,3)21-15-19(16-22(25(21)32)28(4,5)6)34-31(13,14)35-20-17-23(29(7,8)9)26(33)24(18-20)30(10,11)12/h15-18,32-33H,1-14H3
Stdinchikey:FYPMFJGVHOHGLL-UHFFFAOYSA-N
Synonyms:2,6-di-tert-butyl-4-(sulfanyl)phenol

Probucol, sold under the trade name Lorelco among others, is an anti-hyperlipidemic drug[1] initially developed for the treatment of coronary artery disease. Clinical use was discontinued in some countries after it was found that the drug may have the undesired effect of lowering HDL in patients with a previous history of heart disease.[2] [3] It may also cause QT interval prolongation.[3] [4]

Probucol was originally developed as an industrial antioxidant added to tires to maximize their longevity.[5]

Mechanism of action

Probucol lowers the level of cholesterol in the bloodstream by increasing the rate of LDL catabolism. Additionally, probucol may inhibit cholesterol synthesis and delay cholesterol absorption.[6] Probucol is a powerful antioxidant which inhibits the oxidation of cholesterol in LDLs; this slows the formation of foam cells, which form atherosclerotic plaques.

Probucol has also been shown to inhibit ABCA1-dependent cholesterol transport,[7] which may contribute to its known effect of lowering HDL.[8]

Research

Probucol has been found to have antioxidant and anti-inflammatory properties via several different mechanisms.[9] These properties have led to research into the drug's potential capacity to treat sensorineural hearing loss related to oxidative stress,[9] [10] as well as formulations to improve the delivery of the drug into the ear.[10]

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.

Notes and References

  1. Yamamoto A . A Unique Antilipidemic Drug - Probucol . Journal of Atherosclerosis and Thrombosis . 15. 6. 304–5. 11 December 2008. 19075491 . 10.5551/jat.E621 . 2020-01-29. free .
  2. Yamashita S, Masuda D, Matsuzawa Y . Did we abandon probucol too soon? . Current Opinion in Lipidology . 26 . 4 . 304–16 . August 2015 . 26125504 . 10.1097/MOL.0000000000000199 . Probucol has been used as a lipid-lowering drug for a long time especially in Japan, although Western countries quitted its use because of the reduction in serum HDL-cholesterol (HDL-C)..
  3. Yamashita S, Matsuzawa Y . Where are we with probucol: a new life for an old drug? . Atherosclerosis . 207 . 1 . 16–23 . November 2009 . 19457483 . 10.1016/j.atherosclerosis.2009.04.002.
  4. Mamoshina P, Rodriguez B, Bueno-Orovio A . Toward a broader view of mechanisms of drug cardiotoxicity . . 2 . 3 . 100216 . March 2021 . 33763655 . 7974548 . 10.1016/j.xcrm.2021.100216 .
  5. Yamashita S, Masuda D, Matsuzawa Y . New Horizons for Probucol, an Old, Mysterious Drug . Journal of Atherosclerosis and Thrombosis . 28 . 2 . 100–102 . February 2021 . 32507832 . 7957029 . 10.5551/jat.ED132 . Probucol was developed as an anti-oxidative compound to prevent the degradation of tire rubber and later applied to reduce serum LDL-C levels in patients with hypercholesterolemia..
  6. Web site: Probucol (Systemic) . Drugs.com . 1998-08-24 . 2020-01-29.
  7. Favari E, Zanotti I, Zimetti F, Ronda N, Bernini F, Rothblat GH . Probucol inhibits ABCA1-mediated cellular lipid efflux . Arterioscler. Thromb. Vasc. Biol. . 24 . 12 . 2345–50 . 28 October 2004 . 15514211 . 10.1161/01.ATV.0000148706.15947.8a . free .
  8. 10.1016/j.atherosclerosis.2007.12.031 . 18279878 . 200 . 2 . Probucol markedly reduces HDL phospholipids and elevated prebeta1-HDL without delayed conversion into alpha-migrating HDL: putative role of angiopoietin-like protein 3 in probucol-induced HDL remodeling . October 2008 . Atherosclerosis . 329–35 . Miida T, Seino U, Miyazaki O, Hanyu O, Hirayama S, Saito T, Ishikawa Y, Akamatsu S, Nakano T, Katsuyuki N, Okazaki M, Okada M . 2020-01-29.
  9. Chester J, Johnston E, Walker D, Jones M, Ionescu CM, Wagle SR, Kovacevic B, Brown D, Mikov M, Mooranian A, Al-Salami H . A Review on Recent Advancement on Age-Related Hearing Loss: The Applications of Nanotechnology, Drug Pharmacology, and Biotechnology . . 13 . 7 . July 2021 . 1041 . 34371732 . 8309044 . 10.3390/pharmaceutics13071041 . free .
  10. Wagle SR, Ionescu CM, Kovacevic B, Jones M, Foster T, Lim P, Lewkowicz M, Ðanić M, Mikov M, Mooranian A, Al-Salami H . Pharmaceutical characterization of probucol bile acid-lithocholic acid nanoparticles to prevent chronic hearing related and similar cellular oxidative stress pathologies . . 18 . 12 . 923–940 . May 2023 . 37529927 . 10.2217/nnm-2023-0092.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Probucol".

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