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]

Therapeutic Class

Antiarrhythmic Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

322.5

Topological Polar Surface Area (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) [2]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 8.85936 micromolar/kg/day [3]

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

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	[4]

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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	[5]

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Molecular Interaction Atlas (MIA)

MIA Detail

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)

MEA Detail

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	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
3	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
4	Aprindine inhibits calmodulin-stimulated phosphodiesterase and Ca-ATPase activities. J Cardiovasc Pharmacol. 1983 Jan-Feb;5(1):151-6.
5	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.
6	Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
7	Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
8	CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
9	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
10	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
11	Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
12	Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
13	Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
14	Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
15	Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
16	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
17	Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus. Planta Med. 2003 Aug;69(8):692-5.
18	How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
19	The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
20	Calmidazolium evokes high calcium fluctuations in Plasmodium falciparum. Cell Signal. 2016 Mar;28(3):125-135.