Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMBXWU8)

• Drug Name: Aprindine Drug Info
• 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
• Cross-matching ID:
  PubChem CID: 2218
  ChEBI ID: CHEBI:135370
  CAS Number: CAS 37640-71-4
  TTD Drug ID: DMBXWU8
  VARIDT Drug ID: DR00821
  INTEDE Drug ID: DR0126

Molecule-Related Drug Atlas

Drug(s) Targeting Calmodulin (CALM)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Halofantrine	DMOMK1V	Malaria	1F40-1F45	Approved	[9]
Trifluoperazine	DMKBYWI	Anxiety		Approved	[10]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[11]
2-Methyl-2,4-Pentanediol	DMD45CU	Discovery agent	N.A.	Investigative	[11]
MYRISTIC ACID	DMYX0BL	Discovery agent	N.A.	Investigative	[12]
Cacodylate Ion	DMK4XLD	Discovery agent	N.A.	Investigative	[11]
2-Methyl-2-Propanol	DMHM5GJ	Discovery agent	N.A.	Investigative	[11]
N-Trimethyllysine	DMZQXLS	Discovery agent	N.A.	Investigative	[11]
Calmidazolium	DM5ZTJL	Huntington disease	8A01.10	Investigative	[13]

Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[17]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[19]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[20]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[21]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[22]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[23]

Drug(s) Affected By Catalase (CAT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[24]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[25]
Haloperidol	DM96SE0	Delirium		Approved	[26]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[27]
Selenium	DM25CGV	N. A.	N. A.	Approved	[28]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[6]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[29]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[30]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[31]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[32]

Drug(s) Affected By Potassium voltage-gated channel subfamily H member 2 (KCNH2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metoclopramide	DMFA5MY	Nausea	MD90	Approved	[33]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[34]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[35]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[36]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[36]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[37]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[38]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[39]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[40]
Flecainide	DMSQDLE	Tachyarrhythmias	BC71	Approved	[36]

Drug(s) Affected By Angiotensin-converting enzyme 2 (ACE2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Captopril	DM458UM	Chronic heart failure	BD1Z	Approved	[41]
Diazepam	DM08E9O	Alcohol withdrawal		Approved	[42]
Dantrolene	DM1D8XY	Hyperthermia	MG26	Approved	[42]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[42]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[42]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[42]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[42]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[42]
Penicillamine	DM40EF6	Cystinuria	5C60.2	Approved	[42]
Omeprazole	DM471KJ	Cystic fibrosis	CA25	Approved	[42]

Drug(s) Affected By Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[8]
Atenolol	DMNKG1Z	Angina pectoris	BA40	Approved	[8]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[26]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[43]
Bupivacaine	DM4PRFC	Anaesthesia	9A78.6	Approved	[44]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[45]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[46]
Mepivacaine	DMH2NMY	Analgesia	MB40.8	Approved	[44]
Mitoxantrone	DMM39BF	Acute myelogenous leukaemia	2A41	Approved	[47]
Daunorubicin	DMQUSBT	Acute monocytic leukemia		Approved	[47]

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	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Gene/Protein Processing	[5]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Gene/Protein Processing	[6]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[7]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1)	OT8SPJNX	KCNQ1_HUMAN	Drug Response	[8]

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] Aprindine inhibits calmodulin-stimulated phosphodiesterase and Ca-ATPase activities. J Cardiovasc Pharmacol. 1983 Jan-Feb;5(1):151-6.
• [4] 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.
• [5] 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.
• [6] Hepatocellular peroxisomes in human alcoholic and drug-induced hepatitis: a quantitative study. Hepatology. 1991 Nov;14(5):811-7.
• [7] 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.
• [8] 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.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus. Planta Med. 2003 Aug;69(8):692-5.
• [11] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [12] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [13] Calmidazolium evokes high calcium fluctuations in Plasmodium falciparum. Cell Signal. 2016 Mar;28(3):125-135.
• [14] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [15] 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.
• [16] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [21] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [22] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [23] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
• [24] Gypenosides protect retinal pigment epithelium cells from oxidative stress. Food Chem Toxicol. 2018 Feb;112:76-85.
• [25] Role of antioxidant systems in human androgen-independent prostate cancer cells. Prostate. 2000 May 1;43(2):144-9. doi: 10.1002/(sici)1097-0045(20000501)43:2<144::aid-pros9>3.0.co;2-h.
• [26] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [27] Cytotoxic Effects of Cannabinoids on Human HT-29 Colorectal Adenocarcinoma Cells: Different Mechanisms of THC, CBD, and CB83. Int J Mol Sci. 2020 Aug 1;21(15):5533. doi: 10.3390/ijms21155533.
• [28] Selenium deficiency alters epithelial cell morphology and responses to influenza. Free Radic Biol Med. 2007 Jun 15;42(12):1826-37.
• [29] Antioxidant enzyme and malondialdehyde values in social phobia before and after citalopram treatment. Eur Arch Psychiatry Clin Neurosci. 2004 Aug;254(4):231-5.
• [30] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [31] The effect of statins on lipids peroxidation and activities of antioxidants enzymes in patients with dyslipidemia. Przegl Lek. 2006;63(9):738-42.
• [32] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [33] Comparison of the effects of metoclopramide and domperidone on HERG channels. Pharmacology. 2005 Apr;74(1):31-6. doi: 10.1159/000083234. Epub 2005 Jan 7.
• [34] Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol. 2005 Jan;16(1):54-8. doi: 10.1046/j.1540-8167.2005.04470.x.
• [35] Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds. Assay Drug Dev Technol. 2004 Oct;2(5):497-506. doi: 10.1089/adt.2004.2.497.
• [36] Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
• [37] Pharmacology of the short QT syndrome N588K-hERG K+ channel mutation: differential impact on selected class I and class III antiarrhythmic drugs. Br J Pharmacol. 2008 Nov;155(6):957-66. doi: 10.1038/bjp.2008.325. Epub 2008 Aug 25.
• [38] Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy. Br J Pharmacol. 2006 Mar;147(6):642-52. doi: 10.1038/sj.bjp.0706508.
• [39] Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels. Naunyn Schmiedebergs Arch Pharmacol. 1999 Mar;359(3):212-9. doi: 10.1007/pl00005344.
• [40] Redox state dependency of HERGS631C channel pharmacology: relation to C-type inactivation. FEBS Lett. 2000 May 26;474(1):111-5. doi: 10.1016/s0014-5793(00)01586-6.
• [41] Polymorphisms of ACE2 gene are associated with essential hypertension and antihypertensive effects of Captopril in women. Clin Pharmacol Ther. 2007 Aug;82(2):187-96. doi: 10.1038/sj.clpt.6100214. Epub 2007 May 2.
• [42] Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
• [43] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [44] Long QT 1 mutation KCNQ1A344V increases local anesthetic sensitivity of the slowly activating delayed rectifier potassium current. Anesthesiology. 2006 Sep;105(3):511-20. doi: 10.1097/00000542-200609000-00015.
• [45] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [46] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [47] Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment. Arch Toxicol. 2016 Nov;90(11):2763-2777.