Details of the Drug

General Information of Drug (ID: DMK0GHV)

• Drug Name: Encainide
• Synonyms: Encainida; Encainidum; Enkaid; Encainida [Spanish]; Encainide [French]; Encainidum [Latin]; No stereochem; MJ 9067; Encainide (INN); Encainide [INN:BAN]; MJ-9067; MJ-9067-1; Encainide Hydrochloride, (+-)-Isomer; (+-)-2'-[2-(1-methyl-2-piperidyl)ethyl]-p-anisanilide; (+-)-4-Methoxy-N-(2-(2-(1-methyl-2-piperidinyl)ethyl)phenyl)benzamide; (+/-)-4-Methoxy-N-[2-[2-(1-methyl-2-piperidinyl)ethyl]phenyl]benzamide; 4-methoxy-2'-[2-(1-methyl-2-piperidyl)ethyl]benzanilide; 4-methoxy-N-[2-[2-(1-methylpiperidin-2-yl)ethyl]phenyl]benzamide; 4-methoxy-N-{2-[2-(1-methylpiperidin-2-yl)ethyl]phenyl}benzamide

Indication

Disease Entry	ICD 11	Status	REF
Heart arrhythmia	BC65	Withdrawn from market	[1], [2]

• Therapeutic Class: Antiarrhythmic Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 352.5
  Topological Polar Surface Area (xlogp); 4.3
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 13 mL/min/kg [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1 - 2 hours [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 8.1058 micromolar/kg/day [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.26% [4]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 2.2 L/kg [4]
• Chemical Identifiers:
  Formula: C22H28N2O2
  IUPAC Name: 4-methoxy-N-[2-[2-(1-methylpiperidin-2-yl)ethyl]phenyl]benzamide
  Canonical SMILES: CN1CCCCC1CCC2=CC=CC=C2NC(=O)C3=CC=C(C=C3)OC
  InChI: InChI=1S/C22H28N2O2/c1-24-16-6-5-8-19(24)13-10-17-7-3-4-9-21(17)23-22(25)18-11-14-20(26-2)15-12-18/h3-4,7,9,11-12,14-15,19H,5-6,8,10,13,16H2,1-2H3,(H,23,25)
  InChIKey: PJWPNDMDCLXCOM-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 48041
  ChEBI ID: CHEBI:4788
  CAS Number: 66778-36-7
  DrugBank ID: DB01228
  TTD ID: D06PAZ
  INTEDE ID: DR0575

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated sodium channel alpha Nav1.5 (SCN5A)	TTZOVE0	SCN5A_HUMAN	Blocker	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[7]

References

• [1] New antiarrhythmic drugs: tocainide, mexiletine, flecainide, encainide, and amiodarone. Mayo Clin Proc. 1987 Nov;62(11):1033-50.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [6] From first class to third class: recent upheaval in antiarrhythmic therapy--lessons from clinical trials. Am J Cardiol. 1996 Aug 29;78(4A):28-33.
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• [16] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [17] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
• [18] Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders. CNS Drugs. 2009;23(7):555-68.
• [19] Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2000 Dec;11(12):1320-9.
• [20] Medicinal chemistry of neuronal voltage-gated sodium channel blockers. J Med Chem. 2001 Jan 18;44(2):115-37.
• [21] Halothane attenuates the cerebroprotective action of several Na+ and Ca2+ channel blockers via reversal of their ion channel blockade. Eur J Pharmacol. 2002 Oct 4;452(2):175-81.
• [22] Monoamine transporter and sodium channel mechanisms in the rapid pressor response to cocaine. Pharmacol Biochem Behav. 1998 Feb;59(2):305-12.
• [23] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.