Abstract

Probucol has a long history of clinical application with established efficacy and safety profiles. Probucol is a potent anti-oxidant drug that has been in clinical use during the past few decades for the treatment and prevention of cardiovascular diseases. Here we review the current status of knowledge on the pharmacology, clinical benefits, and the mechanism of actions of this unique drug. Probucol has diverse pharmacological properties with therapeutic effects on the cardiovascular systems. Its mechanism of pharmacologic actions at the molecular level has recently been elucidated with the new concept of HDL metabolism associated with cholesteryl ester transfer protein (CETP) or scavenger receptor class B type I (SR-BI). HDL-C reduction may not be a "side effect" but it most likely might reflect a mechanism of action of probucol. Probucol could be reconsidered as an option at least in case statins, which are known to be effective in lowering low-density lipoproteins (LDL) and coronary artery disease (CAD) risk, are not effective. In particular, a marked CAD risk reduction has been recently reported in long-term probucol treatment of patients with heterozygous familial hypercholesterolemia (FH) in Japan. Therefore, probucol could be a more common therapeutic drug for the treatment of patients with FH as well. There is more than enough reason to believe that this old drug has much more to offer than hitherto known.