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Identification
NameAcetyldigitoxin
Accession NumberDB00511  (APRD01334)
TypeSmall Molecule
GroupsApproved
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
Acetylgitaloxin
Acetylgitoxin
alpha-Acetyldigitoxin
alpha-Acetylgitaloxin
alpha-Monoacetyldigitoxin
Desglucolanatoside A
Digitoxin 3'''-acetate
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII0ZV4Q4L2FU
CAS number1111-39-3
WeightAverage: 806.9757
Monoisotopic: 806.44525682
Chemical FormulaC43H66O14
InChI KeyInChIKey=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[[email protected]](CC[C@]4(C)[C@@]3([H])CC[C@]12C)O[[email protected]]1C[[email protected]](O)[[email protected]](O[[email protected]]2C[[email protected]](O)[[email protected]](O[[email protected]]3C[[email protected]](OC(C)=O)[[email protected]](O)[C@@H](C)O3)[C@@H](C)O2)[C@@H](C)O1)C1=CC(=O)OC1
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassSteroid lactones
Direct ParentCardenolide glycosides and derivatives
Alternative Parents
Substituents
  • Cardanolide-glycoside
  • Steroidal glycoside
  • Oligosaccharide
  • Hydroxysteroid
  • Oxane
  • 2-furanone
  • Acetate salt
  • Alpha,beta-unsaturated carboxylic ester
  • Enoate ester
  • Tertiary alcohol
  • Dihydrofuran
  • Cyclic alcohol
  • Secondary alcohol
  • Lactone
  • Carboxylic acid ester
  • Oxacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Acetal
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationUsed for fast digitalization in congestive heart failure.
PharmacodynamicsThe 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 actionAcetyldigitoxin 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.
Related Articles
AbsorptionBioavailability is 60 to 80% following oral administration.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityToxicity 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesC01AA01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

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 the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A1
Uniprot ID:
P05023
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 ]
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Drug created on June 13, 2005 07:24 / Updated on April 28, 2016 16:08