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

General Information of Drug (ID: DMCTE9R)

Drug Name

Mexiletine Drug Info

Synonyms

Mexiletene; Mexiletina; Mexiletinum; Mexilitine; Mexityl; Mexiletine HCL; KO1173; KO-1173; KOE-1173; Mexiletina [INN-Spanish]; Mexiletine (INN); Mexiletine [INN:BAN]; Mexiletinum [INN-Latin]; Mexitil (TN); (+-)-1-(2,6-dimethylphenoxy)propan-2-amine; (2RS)-1-(2,6-dimethylphenoxy)-2-aminopropane; 1-(2',6'-Dimethylphenoxy)-2-aminopropane; 1-(2,6-Dimethylphenoxy)-2-propanamine; 1-(2,6-dimethylphenoxy)propan-2-amine; 1-Methyl-2-(2,6-xylyloxy)ethylamine; 1-methyl-2-(2,6-xylyloxy)ethanamine; 2-(2-Aminopropoxy)-1,3-DiMethyl-Benzene Hydrochloride; 2-(2-aminopropoxy)-1,3-dimethylbenzene

Indication

Disease Entry	ICD 11	Status	REF
Ventricular tachycardia	BC71	Approved	[1]

Therapeutic Class

Antiarrhythmic Agents

Cross-matching ID

PubChem CID: 4178
ChEBI ID: CHEBI:6916
CAS Number: CAS 31828-71-4
TTD Drug ID: DMCTE9R
VARIDT Drug ID: DR00695
INTEDE Drug ID: DR1079
ACDINA Drug ID: D00428

Molecule-Related Drug Atlas

Molecule Type:

DTT

DME

DOT

Drug Status:

Approved Drug(s)

Download the Complete Related Drug List

Drug(s) Targeting Voltage-gated sodium channel alpha Nav1.5 (SCN5A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mephenytoin	DM5UGDK	Epilepsy	8A60-8A68	Approved	[8]
Fosphenytoin	DMOX3LB	Epilepsy	8A60-8A68	Approved	[8]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[2]
LOMERIZINE	DME0TC8	Migraine	8A80	Approved	[9]
Tetrodotoxin	DMWMPRG	Bacterial infection	1A00-1C4Z	Approved	[10]
Dyclonine	DMU6OFP	Pain	MG30-MG3Z	Approved	[11]
Moricizine	DMOMBJW	Arrhythmia	BC9Z	Approved	[12]
Ethotoin	DMXWOCP	Complex partial seizure	8A68.0	Approved	[13]
Prilocaine	DMI7DZ2	Pain	MG30-MG3Z	Approved	[11]
Hexylcaine	DMEADRK	Anaesthesia	9A78.6	Approved	[13]
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Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

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]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]
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Drug(s) Metabolized By Cytochrome P450 1A2 (CYP1A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[23]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[24]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[25]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[26]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[27]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[28]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[29]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[30]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[31]
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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	[32]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[33]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[34]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[22]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[35]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[36]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[37]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[38]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[39]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[58]
Paliperidone	DM7NPJS	Psychotic disorder	6A20-6A25	Approved	[59]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[60]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[61]
Oxatomide	DM1F42Z	Hay fever	CA08.00	Approved	[62]
Cinacalcet	DMCX0K3	Hyperparathyroidism	5A51	Approved	[63]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[64]
Pentamidine	DMHZJCG	African trypanosomiasis	1F51	Approved	[65]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[66]
Buprenorphine	DMPRI8G	Opioid dependence	6C43.2Z	Approved	[67]
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Drug(s) Metabolized By Cytochrome P450 2E1 (CYP2E1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[40]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[41]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[42]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[43]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[44]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[29]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[45]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[46]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[47]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[48]
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Drug(s) Metabolized By Cytochrome P450 2B6 (CYP2B6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[49]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[45]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[50]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[51]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[52]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[53]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[54]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[55]
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[56]
Amitriptyline	DMK7F9S	Depression	6A70-6A7Z	Approved	[57]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated sodium channel alpha Nav1.5 (SCN5A)	TTZOVE0	SCN5A_HUMAN	Blocker	[2]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Substrate	[4]
Cytochrome P450 2D6 (CYP2D6)^{Main DME}	DECB0K3	CP2D6_HUMAN	Substrate	[5]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[6]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Substrate	[4]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Drug Response	[7]

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References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2	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.
3	Pharmacokinetic and pharmacodynamic interaction between mexiletine and propafenone in human beings. Clin Pharmacol Ther. 2000 Jul;68(1):44-57.
4	Role of specific cytochrome P450 enzymes in the N-oxidation of the antiarrhythmic agent mexiletine. Xenobiotica. 2003 Jan;33(1):13-25.
5	Impact of CYP2D6*10 on mexiletine pharmacokinetics in healthy adult volunteers. Eur J Clin Pharmacol. 2003 Sep;59(5-6):395-9.
6	Inhibition of human liver cytochrome P-450 1A2 by the class IB antiarrhythmics mexiletine, lidocaine, and tocainide. J Pharmacol Exp Ther. 1999 May;289(2):853-8.
7	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.
8	Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders. CNS Drugs. 2009;23(7):555-68.
9	Medicinal chemistry of neuronal voltage-gated sodium channel blockers. J Med Chem. 2001 Jan 18;44(2):115-37.
10	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.
11	Monoamine transporter and sodium channel mechanisms in the rapid pressor response to cocaine. Pharmacol Biochem Behav. 1998 Feb;59(2):305-12.
12	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.
13	How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
14	Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
15	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
16	Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
17	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
18	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.
19	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
20	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
21	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
22	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.
23	Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
24	Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
25	Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
26	Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
27	PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
28	The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
29	The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
30	Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
31	Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
32	Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
33	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.
34	CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
35	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.
36	Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
37	Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
38	Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
39	Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
40	Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am J Physiol Gastrointest Liver Physiol. 2005 Jul;289(1):G54-63.
41	Cytochrome P450 2E1 null mice provide novel protection against cisplatin-induced nephrotoxicity and apoptosis. Kidney Int. 2003 May;63(5):1687-96.
42	Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis. 1994 Jan;15(1):5-9.
43	Acetaminophen induced acute liver failure via oxidative stress and JNK activation: protective role of taurine by the suppression of cytochrome P450 2E1. Free Radic Res. 2010 Mar;44(3):340-55.
44	A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes. J Pharmacol Exp Ther. 1998 Sep;286(3):1294-300.
45	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
46	Novel metabolic pathway of estrone and 17beta-estradiol catalyzed by cytochrome P-450. Drug Metab Dispos. 2000 Feb;28(2):110-2.
47	Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes. Biochem Pharmacol. 2002 Oct 1;64(7):1151-6.
48	CYP2E1 and clinical features in alcoholics. Neuropsychobiology. 2003;47(2):86-9.
49	Effect of tamoxifen on the enzymatic activity of human cytochrome CYP2B6. J Pharmacol Exp Ther. 2002 Jun;301(3):945-52.
50	Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96.
51	Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
52	Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
53	Drugs that may have potential CYP2B6 interactions.
54	Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Xenobiotica. 2007 Jul;37(7):717-24.
55	Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone metabolism by cytochrome P450 2B6. Drug Metab Dispos. 2005 Dec;33(12):1760-4.
56	PharmGKB summary: phenytoin pathway. Pharmacogenet Genomics. 2012 Jun;22(6):466-70.
57	Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37.
58	Human recombinant cytochrome P450 enzymes display distinct hydrogen peroxide generating activities during substrate independent NADPH oxidase reactions. Toxicol Sci. 2014 Oct;141(2):344-52. doi: 10.1093/toxsci/kfu133. Epub 2014 Jul 24.
59	Cytochrome P450 2D6 genotype and steady state plasma levels of risperidone and 9-hydroxyrisperidone. Psychopharmacology (Berl). 1999 Dec;147(3):300-5. doi: 10.1007/s002130051171.
60	Effect of penicillin-based antibiotics, amoxicillin, ampicillin, and piperacillin, on drug-metabolizing activities of human hepatic cytochromes P450. J Toxicol Sci. 2016 Feb;41(1):143-6.
61	Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos. 2011 Nov;39(11):2049-56. doi: 10.1124/dmd.111.041384. Epub 2011 Aug 5.
62	Identification of human P450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its kinetic parameters and inhibition constants. Biol Pharm Bull. 2005 Feb;28(2):328-34.
63	Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl. Eur J Clin Pharmacol. 2007 Feb;63(2):159-63.
64	Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities in vitro and in vivo. J Asian Nat Prod Res. 2012;14(4):382-95.
65	Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
66	Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test. Clin Pharmacol Ther. 2001 Oct;70(4):327-35.
67	Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro. Drug Metab Dispos. 2003 Jun;31(6):768-72.