Digitoxin

Digitoxin is a cardiac glycoside that has been found in Digitalis and has diverse biological activities.^1,2,3,4,5 It inhibits human recombinant α₁β₁, α₂β₂, and α₃β₁ subunit-containing Na⁺/K⁺-ATPases with K_i values of 250, 63, and 136 nM, respectively.¹ Digitoxin inhibits the human-ether-a-go-go (hERG) potassium channel, also known as K_v11.1, in HEK293 cells expressing hERG (IC₅₀ = 11.1 nM).² It enhances developed tension and contractile force in electrically stimulated isolated guinea pig left atrial muscle when used at concentrations of 0.2 and 0.4 ?M, respectively.³ Dietary administration of digitoxin (~1 mg/kg per day) attenuates congestive heart failure and reduces myocardial hypertrophy in a rat model of myocardial infarction induced by coronary artery ligation.⁴ Digitoxin is also cytotoxic to a panel of 10 human cancer cell lines, including myeloma, lymphoma, and leukemia cancer cells, with IC₅₀ values ranging from 12 to 76 nM.⁵ Formulations containing digitoxin have previously been used in the treatment of congestive heart failure and cardiac arrhythmias.

1.Katz, A., Lifshitz, Y., Bab-Dinitz, E., et al.Selectivity of digitalis glycosides for isoforms of human Na,K-ATPaseJ. Biol. Chem.285(25)19582-19592(2010) 2.Wang, L., Wible, B.A., Wan, X., et al.Cardiac glycosides as novel inhibitors of human ether-a-go-go-related gene channel traffickingJ. Pharmacol. Exp. Ther.320(2)525-534(2007) 3.Temma, K., Akera, T., and Brody, T.M.Inotropic effects of digitoxin in solated guines-pig heart under conditions which alter contractionEur. J. Pharm.76(4)361-370(1981) 4.Picollo, C.T., dos Santos, A.A., Antonio, E.L., et al.Digitoxin attenuates heart failure, reduces myocardial hypertrophy, and preserves the calcium-binding proteins in infarcted ratsJ. Cardiovasc. Pharmacol. Ther.25(3)265-272(2019) 5.Johansson, S., Lindholm, P., Gullbo, J., et al.Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cellsAnticancer Drugs12(5)475-483(2001)