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Synonym name: Davoxin; Digacin; Dilanacin; Lanoxin; Rougoxin; Digosin; Cordioxil
Catalogue No.: BP0490
Cas No.: 20830-75-5
Formula: C41H64O14
Mol Weight: 780.949
Botanical Source: Digitalis lanata
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.
For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.
Description:
Digoxin is a classical Na,K-ATPase inhibitor, with selectivity for the α2β3 isoform over the common α1β1 isoform, used in the treatment of atrial fibrillation and heart failure. Digoxin and other cardiac glycosides can inhibit hypoxia-inducible factor 1 (HIF-1)α synthesis and block tumor growth.
References:
Lancet. 2015 Jun 13;385(9985):2363-70.
Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in
Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data.
METHODS AND RESULTS:
We studied the use and outcomes of Digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of Digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of Digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767. Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF.
CONCLUSIONS:
This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of Digoxin having these effects. A randomised trial of Digoxin in treatment of AF patients with and without heart failure is needed.
Circ Arrhythm Electrophysiol. 2015 Feb;8(1):49-58.
Digoxin and risk of death in adults with atrial fibrillation: the ATRIA-CVRN study.
Digoxin remains commonly used for rate control in atrial fibrillation, but limited data exist supporting this practice and some studies have shown an association with adverse outcomes. We examined the independent association between Digoxin and risks of death and hospitalization in adults with incident atrial fibrillation and no heart failure.
METHODS AND RESULTS:
We performed a retrospective cohort study of 14,787 age, sex, and high-dimensional propensity score-matched adults with incident atrial fibrillation and no previous heart failure or Digoxin use in the AnTicoagulation and Risk factors In Atrial fibrillation-Cardiovascular Research Network (ATRIA-CVRN) study within Kaiser Permanente Northern and Southern California. We examined the independent association between newly initiated Digoxin and the risks of death and hospitalization using extended Cox regression. During a median 1.17 (interquartile range, 0.49-1.97) years of follow-up among matched patients with atrial fibrillation, incident Digoxin use was associated with higher rates of death (8.3 versus 4.9 per 100 person-years; P<0.001) and hospitalization (60.1 versus 37.2 per 100 person-years; P<0.001). Incident Digoxin use was independently associated with a 71% higher risk of death (hazard ratio, 1.71; 95% confidence interval, 1.52-1.93) and a 63% higher risk of hospitalization (hazard ratio, 1.63; 95% confidence interval, 1.56-1.71). Results were consistent in subgroups of age and sex and when using intent-to-treat or on-treatment analytic approaches.
CONCLUSIONS:
In adults with atrial fibrillation, Digoxin use was independently associated with higher risks of death and hospitalization. Given other available rate control options, Digoxin should be used with caution in the management of atrial fibrillation.
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
203.0600
2.0052
2.0050
.0420
1.1831
2.6431
Low
53.4637
6.1224
No
No
No
No
No
No
0.0
Yes
No
Yes
No
Digoxin, CAS number 20830-75-5, is a classic cardiac glycoside natural product, mainly extracted from the genus Digitalis (Digitalis spp.). As an effective inhibitor of Na⁺/K⁺-ATPase, digoxin holds an important position in cardiovascular diseases, especially in the treatment of heart failure and arrhythmias. Its unique pharmacological mechanism and clinical efficacy make it one of the representative cardiotonic drugs. Although digoxin has a narrow therapeutic window and significant toxic side effects, it still demonstrates irreplaceable value in controlling ventricular rates of atrial fibrillation and improving heart failure symptoms. This paper will systematically review the chemical structure and physicochemical properties of digoxin, plant origin and extraction methods, pharmacological activity, mechanism of action and molecular targets, druggability evaluation, and pharmacokinetic characteristics, and finally explore its clinical application prospects and future development directions.
digoxin is a typical cardiac glycoside compound, with a molecular formula C41H64O14 and a molecular weight of 780.9490. Its structural core is a steroid skeleton, with the C-12 position β-hydroxylated, accompanied by a glycosidic chain composed of three glucose residues. Structurally, digoxin belongs to the digoxin glycoside class, exhibiting dual characteristics of steroid nuclei and glycoside components.
In terms of physicochemical properties, digoxin has a LogP value of about 2.0052, indicating moderate lipid solubility, which facilitates cell membrane penetration. Its polar surface area (TPSA) is 203.0600, and a higher TPSA value suggests strong polarity, affecting its ability to pass through biofilms. Water solubility is relatively low, about 0.0420 mg/mL, limiting the rate and extent of oral absorption. Digoxin has a lower blood-brain barrier penetration capacity, reducing the risk of central nervous system toxicity. The hERG channel inhibition test results were negative, indicating a low risk of direct cardiac electrophysiology and arrhythmias. The Ames test was 0.0, indicating no significant genotoxicity.
Digoxin mainly comes from plants of the genus Digitalis, especially Digitalis lanata and Digitalis purpurea. These plants are widely used in traditional herbal medicine to treat heart diseases. The leaves of foxgone plants are the main accumulation site of digoxin, with relatively high and stable content.
Traditional extraction methods usually use organic solvent extraction such as ethanol or methanol extraction, combined with acid-base adjustment and liquid-liquid distribution technology to further purify digoxin. In modern technology, ultrasound-assisted extraction and supercritical fluid extraction methods are gradually being applied to improve extraction efficiency and purity. The crude extract is separated and purified by liquid chromatography (HPLC) to ensure the quality and activity of digoxin.
In addition, the digoxin content of plant-derived sources is greatly affected by factors such as variety, harvest period, and environmental conditions. Standardized cultivation and extraction processes are crucial to ensuring the stability and safety of medicinal digoxin.
As a cardiac glycoside, digoxin mainly exerts its pharmacological effect by inhibiting Na⁺/K⁺-ATPase on the membrane of myocardial cells. Its cardiotonic effect is manifested by increasing the concentration of sodium ions within myocardial cells, which in turn raises intracellular calcium ion levels through sodium-calcium exchange mechanisms, enhances myocardial contractility, and improves the heart's pumping function.
In arrhythmia treatment, digoxin regulates the autonomic nervous system, reduces atrial conduction velocity, controls the ventricular rate of atrial fibrillation, and decreases the occurrence of arrhythmias. Its antiarrhythmic effects also involve regulation of the electrophysiological properties of myocardial cells.
In recent years, pharmacological research on digoxin has further expanded to include its effects on various molecular targets, such as AMPK (PRKAA1), EHMT2, APP, PTPN1, MAOA, ESR2, etc. These targets are closely related to the pathological mechanisms of heart failure and provide a molecular basis for digoxin's multi-target action.
In addition, digoxin also shows certain potential in regulating apoptosis, oxidative stress, and inflammatory responses, suggesting multidimensional pharmacological effects in the comprehensive treatment of heart failure.
The core mechanism of digoxin is the specific inhibition of Na⁺/K⁺-ATPase (EC 3.6.3.9). Na⁺/K⁺-ATPase is a transmembrane protein on the cell membrane that maintains the sodium-potassium ion gradient inside and outside the cell. Digoxin binds to the α subunit of this enzyme, blocking its activity and causing an increase in intracellular sodium ion concentration.
Elevated sodium concentration affects the function of the sodium-calcium exchanger (NCX), reducing the excretion of calcium ions, promoting intracellular calcium accumulation, and enhancing myocardial contractility. Additionally, digoxin improves heart function by regulating cardiac sympathetic nervous system activity, lowering heart rate and myocardial oxygen consumption.
In terms of molecular targets, besides Na⁺/K⁺-ATPase, digoxin also interacts with various proteins:
The diversity of these molecular targets reflects digoxin's complex pharmacological network, providing theoretical support for its multiple mechanisms of action in cardiovascular disease treatment.
The drug-making evaluation of digoxin shows it has certain potential for drug development, but there are also challenges. It has a relatively large molecular weight (780.9490) and low water solubility (0.0420 mg/mL), which limits its efficiency for oral absorption. The LogP value was 2.0052, indicating moderate lipid solubility that facilitates membrane penetration, but a higher TPSA (203.0600) may affect its transmembrane transport.
The low blood-brain barrier penetration reduces the risk of central nervous system side effects. The hERG channel inhibition test was negative, indicating a low direct risk of arrhythmia. Ames test results showed no significant genotoxicity and good safety.
Pharmacokinetics, digoxin is well absorbed orally, but its bioavailability is greatly affected by gastrointestinal environment and individual differences. It is mainly excreted by the kidneys; patients with renal impairment need to adjust the dosage. Digoxin interacts with multiple drugs, especially drug transport related to P-gp (ABCB1), which affects its plasma concentration.
Digoxin has a narrow therapeutic index, with a small gap between therapeutic dose and toxic dose. Clinical application requires strict monitoring of blood drug concentrations to prevent poisoning. Its pharmacokinetic characteristics and druggability parameters provide important evidence for rational clinical drug use.
As a cardiac glycoside, digoxin has long played an important role in the treatment of heart failure and arrhythmias. By enhancing myocardial contractility and regulating heart rate, it significantly improves patients' clinical symptoms and quality of life.
With advances in molecular biology and pharmacology, digoxin's multi-target mechanism of action has gradually been revealed, providing new ideas for precise drug use in heart failure treatment. In the future, by combining genomics and pharmacogenomics research, personalized digoxin therapy is expected to optimize efficacy and reduce toxic side effects.
In addition, digoxin's potential applications in non-cardiovascular fields such as antitumor and antiviral properties have also attracted widespread attention. Its ability to regulate apoptosis and immune responses makes it possible to develop novel indications.
However, digoxin's narrow treatment window and complex drug interactions remain major limitations in clinical application. Future research should focus on improving drug delivery routes, developing low-toxicity derivatives, and novel formulation technologies to enhance safety and efficacy.
As a classic natural cardiac glycoside, digoxin plays an irreplaceable role in the treatment of heart failure and arrhythmias, thanks to its unique chemical structure and multi-target pharmacological effects. Its mechanism involves inhibition of Na⁺/K⁺-ATPase and regulation of various molecular targets, reflecting a complex pharmacological network.
Despite challenges such as a narrow treatment window and significant toxic side effects, digoxin remains an important component of clinical cardiovascular drugs. In the future, by combining modern pharmacology and molecular biology technologies, in-depth exploration of its mechanisms of action and optimized medication strategies will help enhance the clinical value of digoxin and promote its widespread use in cardiovascular and other disease fields.
Shenshuai
Wenjing
Hedandan
