Identification

Name
Acetyldigitoxin
Accession Number
DB00511  (APRD01334)
Type
Small Molecule
Groups
Approved
Description

Cardioactive derivative of lanatoside A or of digitoxin used for fast digitalization in congestive heart failure.

Structure
Thumb
Synonyms
  • Acetildigitoxina
  • Acetyl-digitoxin-alpha
  • Acetyldiginatin
  • Acetyldigitoxinum
  • Acetylgitoxin
  • alpha-Acetyldigitoxin
  • alpha-Acetylgitaloxin
  • alpha-Monoacetyldigitoxin
  • Desglucolanatoside A
  • Digitoxin 3'''-acetate
Categories
UNII
0ZV4Q4L2FU
CAS number
1111-39-3
Weight
Average: 806.9757
Monoisotopic: 806.44525682
Chemical Formula
C43H66O14
InChI Key
HPMZBILYSWLILX-UMDUKNJSSA-N
InChI
InChI=1S/C43H66O14/c1-21-38(48)33(54-24(4)44)19-37(51-21)57-40-23(3)53-36(18-32(40)46)56-39-22(2)52-35(17-31(39)45)55-27-9-12-41(5)26(16-27)7-8-30-29(41)10-13-42(6)28(11-14-43(30,42)49)25-15-34(47)50-20-25/h15,21-23,26-33,35-40,45-46,48-49H,7-14,16-20H2,1-6H3/t21-,22-,23-,26-,27+,28-,29+,30-,31+,32+,33+,35+,36+,37+,38-,39-,40-,41+,42-,43+/m1/s1
IUPAC Name
(2R,3R,4S,6S)-3-hydroxy-6-{[(2R,3S,4S,6S)-4-hydroxy-6-{[(2R,3S,4S,6R)-4-hydroxy-6-{[(1S,2S,5S,7R,10R,11S,14R,15R)-11-hydroxy-2,15-dimethyl-14-(5-oxo-2,5-dihydrofuran-3-yl)tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-5-yl]oxy}-2-methyloxan-3-yl]oxy}-2-methyloxan-3-yl]oxy}-2-methyloxan-4-yl acetate
SMILES
[H][C@@]1(CC[C@]2(O)[C@]3([H])CC[C@]4([H])C[C@H](CC[C@]4(C)[C@@]3([H])CC[C@]12C)O[C@H]1C[C@H](O)[C@H](O[C@H]2C[C@H](O)[C@H](O[C@H]3C[C@H](OC(C)=O)[C@H](O)[C@@H](C)O3)[C@@H](C)O2)[C@@H](C)O1)C1=CC(=O)OC1

Pharmacology

Indication

Used for fast digitalization in congestive heart failure.

Pharmacodynamics

The main pharmacological effects of acetyldigitoxin are on the heart. Extracardiac effects are responsible for many of the adverse effects. Its main cardiac effects are 1) a decrease of conduction of electrical impulses through the AV node, making it a commonly used drug in controlling the heart rate during atrial fibrillation or atrial flutter, and 2) an increase of force of contraction via inhibition of the Na+/K+ ATPase pump.

Mechanism of action

Acetyldigitoxin binds to a site on the extracellular aspect of the α-subunit of the Na+/K+ ATPase pump in the membranes of heart cells (myocytes). This causes an increase in the level of sodium ions in the myocytes, which then leads to a rise in the level of calcium ions. The proposed mechanism is the following: inhibition of the Na+/K+ pump leads to increased Na+ levels, which in turn slows down the extrusion of Ca2+ via the Na+/Ca2+ exchange pump. Increased amounts of Ca2+ are then stored in the sarcoplasmic reticulum and released by each action potential, which is unchanged by acetyldigitoxin. This is a different mechanism from that of catecholamines. Acetyldigitoxin also increases vagal activity via its central action on the central nervous system, thus decreasing the conduction of electrical impulses through the AV node. This is important for its clinical use in different arrhythmias.

TargetActionsOrganism
ASodium/potassium-transporting ATPase subunit alpha-1
inhibitor
Human
Absorption

Bioavailability is 60 to 80% following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Toxicity includes ventricular tachycardia or ventricular fibrillation, or progressive bradyarrhythmias, or heart block. LD50 = 7.8 mg/kg (orally in mice).

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
10-hydroxycamptothecinAcetyldigitoxin may decrease the cardiotoxic activities of 10-hydroxycamptothecin.
2-(4-Chlorophenyl)-5-QuinoxalinecarboxamideAcetyldigitoxin may decrease the cardiotoxic activities of 2-(4-Chlorophenyl)-5-Quinoxalinecarboxamide.
2-chloroethyl-3-sarcosinamide-1-nitrosoureaAcetyldigitoxin may decrease the cardiotoxic activities of 2-chloroethyl-3-sarcosinamide-1-nitrosourea.
2-MethoxyestradiolAcetyldigitoxin may decrease the cardiotoxic activities of 2-Methoxyestradiol.
3-MethoxybenzamideAcetyldigitoxin may decrease the cardiotoxic activities of 3-Methoxybenzamide.
3,3'-diindolylmethaneAcetyldigitoxin may decrease the cardiotoxic activities of 3,3'-diindolylmethane.
3,4-Dihydroxybenzoic AcidAcetyldigitoxin may decrease the cardiotoxic activities of 3,4-Dihydroxybenzoic Acid.
6-O-benzylguanineAcetyldigitoxin may decrease the cardiotoxic activities of 6-O-benzylguanine.
7-HydroxystaurosporineAcetyldigitoxin may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.
8-azaguanineAcetyldigitoxin may decrease the cardiotoxic activities of 8-azaguanine.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014652
KEGG Drug
D06881
KEGG Compound
C16749
PubChem Compound
5284512
PubChem Substance
46507229
ChemSpider
4447572
ChEBI
53773
ChEMBL
CHEMBL3545057
Therapeutic Targets Database
DAP000119
PharmGKB
PA164746246
Wikipedia
Acetyldigitoxin
ATC Codes
C01AA01 — Acetyldigitoxin

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility0.0274 mg/L at 25 °CMEYLAN,WM et al. (1996)
logP3.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0123 mg/mLALOGPS
logP2.87ALOGPS
logP4.04ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)7.18ChemAxon
pKa (Strongest Basic)0.24ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area188.9 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity200.87 m3·mol-1ChemAxon
Polarizability87.95 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9781
Blood Brain Barrier+0.6297
Caco-2 permeable-0.8308
P-glycoprotein substrateSubstrate0.833
P-glycoprotein inhibitor IInhibitor0.7038
P-glycoprotein inhibitor IIInhibitor0.7664
Renal organic cation transporterNon-inhibitor0.8236
CYP450 2C9 substrateNon-substrate0.8663
CYP450 2D6 substrateNon-substrate0.9191
CYP450 3A4 substrateSubstrate0.7356
CYP450 1A2 substrateNon-inhibitor0.9105
CYP450 2C9 inhibitorNon-inhibitor0.9065
CYP450 2D6 inhibitorNon-inhibitor0.9544
CYP450 2C19 inhibitorNon-inhibitor0.9516
CYP450 3A4 inhibitorNon-inhibitor0.8311
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9302
Ames testNon AMES toxic0.9072
CarcinogenicityNon-carcinogens0.9603
BiodegradationNot ready biodegradable0.9769
Rat acute toxicity4.6091 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9794
hERG inhibition (predictor II)Inhibitor0.6255
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as cardenolide glycosides and derivatives. These are compounds containing a carbohydrate glycosidically bound to the cardenolide moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Steroid lactones
Direct Parent
Cardenolide glycosides and derivatives
Alternative Parents
Steroidal glycosides / Oligosaccharides / 14-hydroxysteroids / O-glycosyl compounds / Oxanes / Butenolides / Dicarboxylic acids and derivatives / Tertiary alcohols / Enoate esters / Secondary alcohols
show 7 more
Substituents
Cardanolide-glycoside / Steroidal glycoside / Oligosaccharide / 14-hydroxysteroid / Hydroxysteroid / Glycosyl compound / O-glycosyl compound / 2-furanone / Dicarboxylic acid or derivatives / Oxane
show 19 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
cardenolide glycoside (CHEBI:53773)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Steroid hormone binding
Specific Function
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates th...
Gene Name
ATP1A1
Uniprot ID
P05023
Uniprot Name
Sodium/potassium-transporting ATPase subunit alpha-1
Molecular Weight
112895.01 Da
References
  1. Gonzalez-Garcia C, Cena V, Klein DC: Characterization of the alpha +-like Na+,K+-ATPase which mediates ouabain inhibition of adrenergic induction of N-acetyltransferase (EC 2.3.1.87) activity: studies with isolated pinealocytes. Mol Pharmacol. 1987 Dec;32(6):792-7. [PubMed:2826993]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 04:22