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]
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Therapeutic Class

Antiarrhythmic Agents

ATC Code

C01BB04: Aprindine

C01BB: Antiarrhythmics, class Ib

C01B: ANTIARRHYTHMICS, CLASS I AND III

C01: CARDIAC THERAPY

C: CARDIOVASCULAR SYSTEM

C01BB04: Aprindine

C01BB: Antiarrhythmics, class Ib

C01B: ANTIARRHYTHMICS, CLASS I AND III

C01: CARDIAC THERAPY

C: CARDIOVASCULAR SYSTEM

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)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

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
UNII: 5Y48085P9Q
DrugBank ID: DB01429
TTD ID: D0W7OE
VARIDT ID: DR00821
INTEDE ID: DR0126

Repurposed Drugs (RPD)

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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]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6)_{Main DME}	DECB0K3	CP2D6_HUMAN	Substrate	[6]

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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]

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Molecular Interaction Atlas (MIA)

MIA Detail

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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)

MEA Detail

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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.