Details of the Drug

General Information of Drug (ID: DMBXWU8)

Drug Name
Aprindine
Synonyms
Aprindin; Aprindina; Aprindinum; Aprinidine; Fibocil; AC 1802; Aprindina [INN-Spanish]; Aprindinum [INN-Latin]; Aprindine (USAN/INN); Aprindine [USAN:BAN:INN]; N-(3-(Diethylamino)propyl)-N-phenyl-2-indanamine; N,N-Diethyl-N'-2-indanyl-N'-phenyl-1,3-propanediamine; N,N-Diethyl-N'-2-indanyl-N'-phenyl-1,3-propanediaminemonohydrochloride; N'-(2,3-dihydro-1H-inden-2-yl)-N,N-diethyl-N'-phenylpropane-1,3-diamine; N-(2,3-Dihydro-1H-inden-2-yl)-N',N'-diethyl-N-phenyl-1,3-propanediamine; N-(2,3-dihydro-1H-inden-2-yl)-N',N'-diethyl-N-phenylpropane-1,3-diamine
Indication
Disease Entry ICD 11 Status REF
Cardiac arrhythmias BC9Z Approved [1]
Long QT syndrome BC65.0 Approved [2]
Therapeutic Class
Antiarrhythmic Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 322.5
Logarithm of the Partition Coefficient (xlogp) 5.2
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
Bioavailability
85% of drug becomes completely available to its intended biological destination(s) [3]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 8.85936 micromolar/kg/day [4]
Chemical Identifiers
Formula
C22H30N2
IUPAC Name
N'-(2,3-dihydro-1H-inden-2-yl)-N,N-diethyl-N'-phenylpropane-1,3-diamine
Canonical SMILES
CCN(CC)CCCN(C1CC2=CC=CC=C2C1)C3=CC=CC=C3
InChI
InChI=1S/C22H30N2/c1-3-23(4-2)15-10-16-24(21-13-6-5-7-14-21)22-17-19-11-8-9-12-20(19)18-22/h5-9,11-14,22H,3-4,10,15-18H2,1-2H3
InChIKey
NZLBHDRPUJLHCE-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
2218
ChEBI ID
CHEBI:135370
CAS Number
37640-71-4
DrugBank ID
DB01429
TTD ID
D0W7OE
VARIDT ID
DR00821
INTEDE ID
DR0126
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Calmodulin (CALM) TTV3NH6 CALM1_HUMAN ; CALM2_HUMAN ; CALM3_HUMAN Inhibitor [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2D6 (CYP2D6)
Main DME 		DECB0K3 CP2D6_HUMAN Substrate [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Gene/Protein Processing [7]
Catalase (CAT) OTHEBX9R CATA_HUMAN Gene/Protein Processing [8]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Gene/Protein Processing [9]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) OT8SPJNX KCNQ1_HUMAN Drug Response [10]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Cardiac arrhythmias
ICD Disease Classification BC9Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Calmodulin (CALM) DTT CALM 6.44E-01 0.09 0.15
Calmodulin (CALM) DTT CALM 5.89E-01 -3.28E-04 -1.09E-03
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 2.59E-01 6.29E-02 3.14E-01
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 4.84E-01 -8.38E-02 -8.46E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Appropriate dosing of antiarrhythmic drugs in Japan requires therapeutic drug monitoring. J Clin Pharm Ther. 2005 Feb;30(1):5-12.
2 Time-to-Onset Analysis of Drug-Induced Long QT Syndrome Based on a Spontaneous Reporting System for Adverse Drug Events. PLoS One. 2016 Oct 10;11(10):e0164309.
3 Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
4 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
5 Aprindine inhibits calmodulin-stimulated phosphodiesterase and Ca-ATPase activities. J Cardiovasc Pharmacol. 1983 Jan-Feb;5(1):151-6.
6 Nonlinear mixed effects model analysis of the pharmacokinetics of routinely administered bepridil in Japanese patients with arrhythmias. Biol Pharm Bull. 2006 Mar;29(3):517-21.
7 Prediction of off-target effects on angiotensin-converting enzyme 2. J Biomol Screen. 2011 Sep;16(8):878-85. doi: 10.1177/1087057111413919. Epub 2011 Aug 22.
8 Hepatocellular peroxisomes in human alcoholic and drug-induced hepatitis: a quantitative study. Hepatology. 1991 Nov;14(5):811-7.
9 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
10 Additional gene variants reduce effectiveness of beta-blockers in the LQT1 form of long QT syndrome. J Cardiovasc Electrophysiol. 2004 Feb;15(2):190-9. doi: 10.1046/j.1540-8167.2004.03212.x.