DrugBank: Acetyldigitoxin (DB00511)

targets (1)

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Not Available

Brand names

Acigoxin
Acylanid
Crystodigin

Brand name mixtures

Not Available

Categories

Enzyme Inhibitors
Cardiotonic Agents
Anti-Arrhythmia Agents

CAS number

25395-32-8

Weight

Average: 806.9757
Monoisotopic: 806.445256820

Chemical Formula

C₄₃H₆₆O₁₄

InChI Key

InChIKey=HPMZBILYSWLILX-NUZCUNEWSA-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

Plain Text

IUPAC Name

(2R,3R,4S,6S)-3-hydroxy-6-{[(2R,4S,6S)-4-hydroxy-6-{[(2R,3S,4S,6R)-4-hydroxy-6-{[(1S,2S,7R,10R,11S,14R,15R)-11-hydroxy-2,15-dimethyl-14-(5-oxo-2,5-dihydrofuran-3-yl)tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan-5-yl]oxy}-2-methyloxan-3-yl]oxy}-2-methyloxan-3-yl]oxy}-2-methyloxan-4-yl acetate

SMILES

[H][C@]12CC[C@]3([H])[C@]([H])(CC[C@]4(C)[C@H](CC[C@]34O)C3=CC(=O)OC3)[C@@]1(C)CCC(C2)O[C@H]1C[C@H](O)[C@H](O[C@H]2C[C@H](O)C(O[C@H]3C[C@H](OC(C)=O)[C@H](O)[C@@H](C)O3)[C@@H](C)O2)[C@@H](C)O1

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Steroids and Steroid Derivatives

Substructures

Steroids and Steroid Derivatives
Carboxylic Acids and Derivatives
Glycerol and Derivatives
Hydroxy Compounds
Alkanes and Alkenes
Pyrans
Acetates
Acetals and Derivatives
Sterols
Lactones
Ethers
Bicyclohexanes
Alcohols and Polyols
Heterocyclic compounds

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.

Absorption

Bioavailability is 60 to 80% following oral administration.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

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

Pharmacoeconomics

Manufacturers

Novartis pharmaceuticals corp

Packagers

Not Available

Dosage forms

Form	Route	Strength
Injection	Intravenous

Prices

Not Available

Patents

Not Available

Properties

State

solid

Melting point

Not Available

Experimental Properties

Property	Value	Source
water solubility	0.0274 mg/L at 25 oC [MEYLAN,WM et al. (1996)]	PhysProp
logP	3.7	PhysProp

Predicted Properties

Property	Value	Source
water solubility	1.23e-02 g/l	ALOGPS
logP	2.87	ALOGPS
logP	4.04	ChemAxon Molconvert
logS	-4.82	ALOGPS
pKa	13.06	ChemAxon Molconvert
hydrogen acceptor count	12	ChemAxon Molconvert
hydrogen donor count	4	ChemAxon Molconvert
polar surface area	188.90	ChemAxon Molconvert
rotatable bond count	9	ChemAxon Molconvert
refractivity	200.87	ChemAxon Molconvert
polarizability	88.17	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D06881
PubChem Compound	68949
PubChem Substance	46507229
ChemSpider	62172
ChEBI	53773
ChEMBL	53773
Therapeutic Targets Database	DAP000119
Drug Product Database	0
Wikipedia	http://en.wikipedia.org/wiki/Acetyldigitoxin

ATC Codes

C01AA01

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Drug	Interaction

Food Interactions

Not Available

Targets
1. Sodium/potassium-transporting ATPase alpha-1 chain Pharmacological action: yes Actions: inhibitor 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 Organism class: human UniProt ID: P05023 Gene: ATP1A1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Targets

1. Sodium/potassium-transporting ATPase alpha-1 chain

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P05023 Link_out

Gene: ATP1A1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Comments

Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:04

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.