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Digoxin as an emerging therapy in noncardiac diseases

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Abstract

The cardiac glycoside (CG) digoxin is a generic drug approved for the treatment of heart failure and supraventricular arrhythmias. Over the past few decades, substantial strides have been made toward repurposing digoxin to treat various noncardiac diseases. Here, we evaluate recent insights into basic and clinical work related to noncardiac use of digoxin.

Section snippets

Overview of digoxin and drug repurposing

Digoxin is a CG (see Glossary) isolated from the purple foxglove Digitalis purpurea. Like other CGs, the structure of digoxin is conserved. CGs consist of a steroid ring bound to a lactone ring at position 17, with or without a sugar moiety at position 3. The steroid ring is present in all CGs and consists of 17 carbons arranged in four rings. The diversity of CGs arises from the number of carbons in the lactone ring, which determines their activity, and their associated sugar moieties, which

Concluding remarks and future directions

Repurposing of the CG digoxin for noncardiac indications is a very attractive strategy for several reasons, including cost and time savings. Digoxin has several decades of use in the cardiac arena; hence, knowledge accrued from its clinical use can be applied toward its repurposing for noncardiac diseases. Central to the well-known biologic activity of digoxin is its inhibitory effect on the Na,K-ATPase pump. Aside from its pump function, the Na,K-ATPase also functions as a signal transducer, a

Acknowledgments

Research in W.Z.M.’s laboratory is supported by National Institutes of Health U01 grant 5U01AA026962-02.

Declaration of interests

No interests are declared.

Glossary

Cardiac glycoside (CG)
a class of compounds that inhibit the Na,K-ATPase enzyme, increasing the output force of the heart and decreasing its rate of contractions. These properties are beneficial for treatment of congestive heart failure and cardiac arrhythmias.
Cytokine storm
a potentially harmful exaggerated immune response during which the body releases a large number of cytokines concurrently into the bloodstream, typically in response to infection or immune therapy.
Drug repurposing
a process of

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