DT-Web

DB00511 - Acetyldigitoxin


Identification
Name Acetyldigitoxin
Accession Number DB00511 (APRD01334)
Type small molecule
Description Cardioactive derivative of lanatoside A or of digitoxin used for fast digitalization in congestive heart failure.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 806.9757
Groups approved
Monoisotopic Weight 806.44525682
Pharmacology
Indication Used for fast digitalization in congestive heart failure.
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.
Protein binding Not Available
Biotransformation Not Available
Route of elimination 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
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Sodium/potassium-transporting ATPase alpha-1 chain
Name Sodium/potassium-transporting ATPase alpha-1 chain
Gene Name ATP1A1
Pharmacological action yes
Actions inhibitor
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
DTHybrid score 0.7588

Predictions


Id Partner name Gene Name Score
566 Serotransferrin TF 0.0538
558 Solute carrier family 12 member 1 SLC12A1 0.0385
295 Carbonic anhydrase 1 CA1 0.0298
6150 Solute carrier organic anion transporter family member 4C1 SLCO4C1 0.028
357 Carbonic anhydrase 2 CA2 0.0223
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.0221
592 Carbonic anhydrase 4 CA4 0.0214
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0187
3932 Glutathione S-transferase A2 GSTA2 0.017
587 Serum albumin ALB 0.0164
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0156
1405 Thiopurine S-methyltransferase TPMT 0.0148
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0143
466 Solute carrier family 12 member 3 SLC12A3 0.0124
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0124
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0123
1588 Multidrug resistance protein 1 ABCB1 0.0123
3426 Glutamine synthetase glnA 0.0121
3987 Glutamine synthetase GLUL 0.0121
4205 Carbonic anhydrase 9 CA9 0.0118
3007 Carbonic anhydrase 12 CA12 0.0118
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0108
741 Potassium voltage-gated channel subfamily KQT member 1 KCNQ1 0.0103
6142 Solute carrier family 22 member 8 SLC22A8 0.0102
1729 Solute carrier family 22 member 6 SLC22A6 0.0098
6047 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A PDE1A 0.0093
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0087
392 Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A 0.0087
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 0.0081
4160 Voltage-dependent calcium channel subunit alpha-2/delta-2 CACNA2D2 0.008
4512 Cytochrome P450 3A4 CYP3A4 0.0076
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0073
6167 Organic solute transporter subunit beta OSTB 0.0066
6166 Organic solute transporter subunit alpha OSTA 0.0066
6024 Cytochrome P450 1A1 CYP1A1 0.0065
465 Calmodulin CALM1 0.0062
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0054
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0042
776 Bile salt export pump ABCB11 0.0041
4119 Cytochrome P450 2D6 CYP2D6 0.0037
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