Identification

Name
Indecainide
Accession Number
DB00192  (APRD01032)
Type
Small Molecule
Groups
Approved
Description

Indecainide is a rarely used antidysrhythmic. Indecainide has local anesthetic activity and belongs to the membrane stabilizing (Class 1) group of antiarrhythmic agents; it has electrophysiologic effects characteristic of the IC class of antiarrhythmics.

Structure
Thumb
Synonyms
  • Indecainida
  • Indecainide
  • Indecainidum
Product Ingredients
IngredientUNIICASInChI Key
Indecainide hydrochlorideM76V0B96L573681-12-6NXNSCUZKMVYAJQ-UHFFFAOYSA-N
International/Other Brands
Decabid (Eli Lilly)
Categories
Not Available
UNII
3AZF20DM1T
CAS number
74517-78-5
Weight
Average: 308.4174
Monoisotopic: 308.1888634
Chemical Formula
C20H24N2O
InChI Key
UCEWGESNIULAGX-UHFFFAOYSA-N
InChI
InChI=1S/C20H24N2O/c1-14(2)22-13-7-12-20(19(21)23)17-10-5-3-8-15(17)16-9-4-6-11-18(16)20/h3-6,8-11,14,22H,7,12-13H2,1-2H3,(H2,21,23)
IUPAC Name
9-{3-[(propan-2-yl)amino]propyl}-9H-fluorene-9-carboxamide
SMILES
CC(C)NCCCC1(C(N)=O)C2=CC=CC=C2C2=CC=CC=C12

Pharmacology

Indication

For the treatment of life-threatening dysrhythmias and sustained ventricular tachycardia.

Pharmacodynamics

Indecainide is a rarely used antidysrhythmic. Indecainide has local anesthetic activity and belongs to the membrane stabilizing (Class 1) group of antiarrhythmic agents; it has electrophysiologic effects characteristic of the IC class of antiarrhythmics.

Mechanism of action

Indecainide acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers.

TargetActionsOrganism
ASodium channel protein type 5 subunit alpha
inhibitor
Human
Absorption

Nearly complete 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

When given orally to either young adult rats or mice, the LD50 was 100 mg/kg. Symptoms of overdose include nausea and vomiting, convulsions, hypotension, bradycardia, syncope, extreme widening of the QRS complex, widening of the QT interval, widening of the PR interval, ventricular tachycardia, AV nodal block, asystole, bundle branch block, cardiac failure, and cardiac arrest.

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

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Giardina EV, Saroff AL, Schneider M: Effect of indecainide in patients with left ventricular dysfunction. Clin Pharmacol Ther. 1990 Nov;48(5):582-9. [PubMed:2225716]
External Links
Human Metabolome Database
HMDB0014338
PubChem Compound
52195
PubChem Substance
46506714
ChemSpider
47194
ChEBI
135314
ChEMBL
CHEMBL1201242
Therapeutic Targets Database
DAP000503
PharmGKB
PA164754881
Wikipedia
Indecainide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)94-95 °CPhysProp
water solubility1.88 mg/LNot Available
logP3.11MANNHOLD,R ET AL. (1990)
Predicted Properties
PropertyValueSource
Water Solubility0.000896 mg/mLALOGPS
logP3.24ALOGPS
logP3.26ChemAxon
logS-5.5ALOGPS
pKa (Strongest Acidic)16.51ChemAxon
pKa (Strongest Basic)10.4ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area55.12 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity94.05 m3·mol-1ChemAxon
Polarizability35.56 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9955
Blood Brain Barrier+0.994
Caco-2 permeable+0.5527
P-glycoprotein substrateSubstrate0.7322
P-glycoprotein inhibitor INon-inhibitor0.7405
P-glycoprotein inhibitor IINon-inhibitor0.8525
Renal organic cation transporterNon-inhibitor0.6101
CYP450 2C9 substrateNon-substrate0.8006
CYP450 2D6 substrateNon-substrate0.6619
CYP450 3A4 substrateSubstrate0.5911
CYP450 1A2 substrateInhibitor0.5715
CYP450 2C9 inhibitorNon-inhibitor0.6947
CYP450 2D6 inhibitorNon-inhibitor0.6213
CYP450 2C19 inhibitorInhibitor0.5978
CYP450 3A4 inhibitorNon-inhibitor0.5383
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6169
Ames testNon AMES toxic0.822
CarcinogenicityNon-carcinogens0.8477
BiodegradationNot ready biodegradable0.9814
Rat acute toxicity2.3529 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9977
hERG inhibition (predictor II)Inhibitor0.6032
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 fluorenes. These are compounds containing a fluorene moiety, which consists of two benzene rings connected through either a cyclopentane, cyclopentene, or cyclopenta-1,3-diene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Fluorenes
Sub Class
Not Available
Direct Parent
Fluorenes
Alternative Parents
Delta amino acids and derivatives / Aralkylamines / Fatty amides / Primary carboxylic acid amides / Dialkylamines / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Delta amino acid or derivatives / Fluorene / Aralkylamine / Fatty amide / Fatty acyl / Amino acid or derivatives / Carboxamide group / Primary carboxylic acid amide / Carboxylic acid derivative / Secondary aliphatic amine
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  4. Jaillon P, Drici M: Recent antiarrhythmic drugs. Am J Cardiol. 1989 Dec 5;64(20):65J-69J. [PubMed:2688391]
  5. Holland DR, Lacefield WB, Gonzales CR, Johnston SR, Turk JA: Indecainide: effects on arrhythmias, electrophysiology, and cardiovascular dynamics. J Cardiovasc Pharmacol. 1989 Sep;14(3):454-61. [PubMed:2476626]
  6. Steinberg MI, Wiest SA: Electrophysiological studies of indecainide hydrochloride, a new antiarrhythmic agent, in canine cardiac tissues. J Cardiovasc Pharmacol. 1984 Jul-Aug;6(4):614-21. [PubMed:6206315]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 16:30