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Pleiotropic Effects of Cardioactive Glycosides

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Abstract:

Cardioactive glycosides, like digoxin, ouabain and related compounds, are drugs that inhibit Na+/K+-ATPase and have a strong inotropic effect on heart: they cause the Na+/Ca2+ exchanger to extrude Na+ in exchange with Ca2+ and therefore increase the [Ca2+]i concentration. For this reason, some of these drugs are currently used in the treatment of congestive heart failure and cardiac arrhythmias. Recently it has been discovered that cardiac glycosides exert pleiotropic effects on many aspects of cell metabolism. Na+/K+-ATPase is not the exclusive target, as they affect the cell response to hypoxia, modulate several signaling pathways involved in cell death and proliferation, regulate the transcription of different genes and modify the pharmacokinetics of other drugs, by altering the expression and activity of drug-metabolizing enzymes. Some of these effects are related to the steroid structure of glycosides, a property which also makes them fine modulators of the synthesis of cholesterol and steroid hormones. Moreover, new endogenously synthesized glycosides have been discovered in the last years: these molecules are involved in the balance of salt and in the control of blood pressure.

This review will focus on the recent studies which have demonstrated that exogenous and endogenous glycosides, besides playing a role as inotropic agents, are also important in the pathogenesis and therapy of different human diseases, such as stroke, diabetes, neurological diseases and cancer.



Keywords: Cardioactive glycosides; Digoxin; Na+/K+-ATPase; cancer; cardiac arrhythmias; ouabain; pleiotropic effects; roliferation; sterols metabolism

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986711794927685

Publication date: February 1, 2011

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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