MEXILETINE

First approved in 1985

Details

Stereochemistry	RACEMIC
Molecular Formula	C11H17NO
Molecular Weight	179.2588
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(N)COC1=C(C)C=CC=C1C

InChI

InChIKey=VLPIATFUUWWMKC-UHFFFAOYSA-N

InChI=1S/C11H17NO/c1-8-5-4-6-9(2)11(8)13-7-10(3)12/h4-6,10H,7,12H2,1-3H3

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/74865ap_appltr_prntlbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/26068619 | https://www.ncbi.nlm.nih.gov/pubmed/26068619

Mexiletine is a non-selective voltage-gated sodium channel blocker which belongs to the Class IB anti-arrhythmic group of medicines. It is used to treat heart arrhythmias. Mexiletine is also used to treat refractory pain and muscle stiffness resulting in myotonic dystrophy or myotonia congenita. Mexiletine was approved for commercial use in 1985 under the brand name Mexitil, but most marketing efforts have since been discontinued. There has been a continued effort to identify other therapeutic use cases and a number of clinical trials have been conducted including ALS and chronic pain from amputation.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium channel protein type 5 subunit alpha 9 Target ID: Q14524\|\|\|E9PFW7 Gene ID: 6331.0 Gene Symbol: SCN5A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/16168489	Blocker 537
Sodium channel protein type 9 subunit alpha 3 Target ID: Q15858\|\|\|Q8WWN4 Gene ID: 6335.0 Gene Symbol: SCN9A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26068619	Blocker 537

Conditions

Condition	Modality	Highest Phase	Product
Life-threatening arrhythmias 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/74865ap_appltr_prntlbl.pdf	Primary	Approved 8429	MEXITIL Approved Use Mexiletine hydrochloride capsules are indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that, in the judgment of the physician, are life-threatening. Because of the proarrhythmic effects of mexiletine, its use with lesser arrhythmias is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided. Initiation of mexiletine treatment, as with other antiarrhythmic agents used to treat life-threatening arrhythmias, should be carried out in the hospital. Antiarrhythmic drugs have not been shown to enhance survival in patients with ventricular arrhythmias. Launch Date 1985
Muscle cramps in amyotrophic lateral sclerosis 2 Sources: https://clinicaltrials.gov/ct2/show/NCT01811355	Primary	Approved 8429	MEXITIL Approved Use Mexiletine hydrochloride capsules are indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that, in the judgment of the physician, are life-threatening. Because of the proarrhythmic effects of mexiletine, its use with lesser arrhythmias is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided. Initiation of mexiletine treatment, as with other antiarrhythmic agents used to treat life-threatening arrhythmias, should be carried out in the hospital. Antiarrhythmic drugs have not been shown to enhance survival in patients with ventricular arrhythmias. Launch Date 1985
Chronic pain from amputation 2 Sources: https://clinicaltrials.gov/ct2/show/NCT00383682	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
0.21 μg/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.2 μg/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	200 mg 3 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MEXILETINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.59 μg/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	100 mg 3 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MEXILETINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.35 μg/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.46 μg/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.45 μg/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.81 μg/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
2.96 μg × h/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
22 μg × h/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	200 mg 3 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MEXILETINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3.7 μg × h/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	100 mg 3 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MEXILETINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5.8 μg × h/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
6.7 μg × h/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
7.76 μg × h/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
8.3 μg × h/mL REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
9.4 h REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9.9 h REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	200 mg 3 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MEXILETINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
14.1 h REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	100 mg 3 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MEXILETINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
10.8 h REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
10 h REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
11.1 h REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
7 h REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	MEXILETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
40% REVIEW https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		MEXILETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
500 mg single, intramuscular Highest studied dose Dose: 500 mg Route: intramuscular Route: single Dose: 500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/2419687 Page: p.24, 25	unhealthy, 55-78 n = 9 Health Status: unhealthy Condition: Myocardial infarction Age Group: 55-78 Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/2419687 Page: p.24, 25	Sources: https://pubmed.ncbi.nlm.nih.gov/2419687 Page: p.24, 25
400 mg 3 times / day multiple, oral MTD Dose: 400 mg, 3 times / day Route: oral Route: multiple Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2451577 Page: p.132	unhealthy, 55.5 n = 16 Health Status: unhealthy Condition: Ventricular arrhythmias Age Group: 55.5 Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/2451577 Page: p.132	Sources: https://pubmed.ncbi.nlm.nih.gov/2451577 Page: p.132
200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.105, 106, 112	unhealthy n = 25 Health Status: unhealthy Condition: Myotonic disorders Population Size: 25 Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.105, 106, 112	Disc. AE: Tachycardia... AEs leading to discontinuation/dose reduction: Tachycardia (severe, 4%) Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.105, 106, 112
200 mg 3 times / day multiple, oral (max) Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.109	unhealthy n = 39 Health Status: unhealthy Condition: Myotonic disorders Population Size: 39 Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.109	Disc. AE: Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (2.6%) Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.109
200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.109	unhealthy n = 58 Health Status: unhealthy Condition: Myotonic disorders Population Size: 58 Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.109	Disc. AE: Migraine, Gastrointestinal discomfort... AEs leading to discontinuation/dose reduction: Migraine (1.7%) Gastrointestinal discomfort (1.7%) Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.109

AEs

AE	Significance	Dose	Population
Tachycardia	severe, 4% Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.105, 106, 112	unhealthy n = 25 Health Status: unhealthy Condition: Myotonic disorders Population Size: 25 Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.105, 106, 112
Diarrhea	2.6% Disc. AE	200 mg 3 times / day multiple, oral (max) Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.109	unhealthy n = 39 Health Status: unhealthy Condition: Myotonic disorders Population Size: 39 Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.109
Gastrointestinal discomfort	1.7% Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.109	unhealthy n = 58 Health Status: unhealthy Condition: Myotonic disorders Population Size: 58 Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.109
Migraine	1.7% Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.109	unhealthy n = 58 Health Status: unhealthy Condition: Myotonic disorders Population Size: 58 Sources: https://www.ema.europa.eu/en/documents/assessment-report/namuscla-epar-public-assessment-report_en.pdf Page: p.109

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Cav1.2 45	CYP1A2 1054 CYP 270

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/018873Orig1s000rev.pdf Page: 18, 44	likely
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/18873slr018ltr.pdf Page: 1, 2	major
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/18873slr018ltr.pdf Page: 1, 2	minor	yes (co-administration study) Comment: coadminitration with fluvoxamine decreased mexiletine clearance by 38% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/18873slr018ltr.pdf Page: 1, 2

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 49	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/23580742/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879774/
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/26516576/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6916	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6916
ChemicalBook	CB22750077	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB22750077
ChemicalBook	CB9497353	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9497353
eMolecules	1012300	https://www.emolecules.com/cgi-bin/more?vid=1012300

PubMed

Title	Date	PubMed
Mexiletine in the treatment of ventricular arrhythmias.	1980	6966452
Torsades de pointes as a manifestation of mexiletine toxicity.	1980 Dec	7446392
New drugs for treating cardiac arrhythmias.	1981 Jan	6780988
[Mexiletine in the treatment of lidocaine-resistant ventricular tachycardia. Preliminary results].	1982	7160572
Mexiletine in refractory ventricular arrhythmias.	1983 Dec	6641093
Drug interactions with amiodarone.	1983 Oct	6137140
International mexiletine and placebo antiarrhythmic coronary trial: I. Report on arrhythmia and other findings. Impact Research Group.	1984 Dec	6209318
Hemodynamic effects of mexiletine.	1984 May	6372422
Facilitation of ventricular tachyarrhythmia induction by isoproterenol.	1984 Oct 1	6486026
Mexiletine for recurring ventricular arrhythmias: assessment by long-term electrocardiographic recordings and sequential electrophysiologic studies.	1984 Sep	6475711
Inhibition of sympathetic nervous system by mexiletine, an antiarrhythmic agent, and its antagonism against ouabain.	1985	4039173
Mexiletine: long-term follow-up of a patient with prolonged QT interval and quinidine-induced torsades de pointes.	1985 Feb	3919448
[Anti-arrhythmic efficacy of the amiodarone-mexiletine combination in the treatment of resistant complex ventricular arrhythmias].	1986 May	3732727
Comparative efficacy and safety of oral mexiletine and quinidine in benign or potentially lethal ventricular arrhythmias.	1987 Dec 1	3318368
[2 cases of lidocaine-resistant ventricular tachycardia treated with i.v. mexiletine during complicated acute myocardial infarct].	1987 Nov 30	2972491
General pharmacological studies on N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate. 1st communication: effect on the central nervous system.	1988 Oct	3196380
Differentiation and mechanisms of prevention and termination of verapamil-sensitive sustained ventricular tachycardia.	1989 Dec 5	2480708
Cardioprotective effects of various class I antiarrhythmic drugs in canine hearts.	1989 Jul	2738264
Broad sensitivity of rodent arrhythmia models to class I, II, III, and IV antiarrhythmic agents.	1989 Jun	2726785
Congestive heart failure induced by six of the newer antiarrhythmic drugs.	1989 Nov 1	2509529
Combined application of class I antiarrhythmic drugs causes "additive", "reductive", or "synergistic" sodium channel block in cardiac muscles.	1990 Nov	2176934
Long-term effect of mexiletine on left ventricular function and relation to suppression of ventricular arrhythmia.	1990 Nov 15	1700592
Mexiletine-associated left ventricular dysfunction: a case study.	1991 Jun	1861579
Mexiletine's antifibrillatory actions are limited by the occurrence of convulsions in conscious animals.	1992 Jan 21	1612103
Neurotoxicity of lidocaine combined with mexiletine.	1993 Dec	8250327
Usefulness of oral quinidine-mexiletine combination therapy for sustained ventricular tachyarrhythmias as assessed by programmed electrical stimulation when quinidine monotherapy has failed.	1994 Apr	8154423
Mexiletine-induced severe skin eruption, fever, eosinophilia, atypical lymphocytosis, and liver dysfunction.	1997 Oct	9414061
Lack of stereoselectivity for the antiallodynic effect of mexiletine in spinally injured rats.	2000	11124013
Effects of mexiletine on the canine cardiovascular system complicating cisapride overdose: potential utility of mexiletine for the treatment of drug-induced long QT syndrome.	2000 Aug	11001179
Effect of oral mexiletine on capsaicin-induced allodynia and hyperalgesia: a double-blind, placebo-controlled, crossover study.	2000 Sep-Oct	11009231
Efficacy of oral mexiletine for neuropathic pain with allodynia: a double-blind, placebo-controlled, crossover study.	2000 Sep-Oct	11009230
Schwartz-Jampel syndrome: report of one case.	2002 Jul-Aug	12238912
Effects of mexiletine on the canine model of sparfloxacin-induced long QT syndrome.	2003 Aug 22	12969756
Mexiletine block of wild-type and inactivation-deficient human skeletal muscle hNav1.4 Na+ channels.	2004 Feb 1	14608007
Antinociceptive effects of sodium channel-blocking agents on acute pain in mice.	2004 Jun	15215642
Analysis of human Nav1.8 expressed in SH-SY5Y neuroblastoma cells.	2005 Dec 28	16325806
Effect of mexiletine on vincristine-induced painful neuropathy in mice.	2006 Apr 24	16556439
Digoxin and mexiletine sensitivity in a Collie with the MDR1 mutation.	2006 Mar-Apr	16594604
Experimental studies of potential analgesics for the treatment of chemotherapy-evoked painful peripheral neuropathies.	2008 Jul-Aug	18777607
Pharmacological characterization and gene expression profiling of an L5/L6 spinal nerve ligation model for neuropathic pain in mice.	2008 May 2	18400411
In utero onset of long QT syndrome with atrioventricular block and spontaneous or lidocaine-induced ventricular tachycardia: compound effects of hERG pore region mutation and SCN5A N-terminus variant.	2008 Nov	18848812
Mexiletine-responsive erythromelalgia due to a new Na(v)1.7 mutation showing use-dependent current fall-off.	2009 Apr	19162012
Effects of antiarrhythmic drugs on the hyperpolarization-activated cyclic nucleotide-gated channel current.	2009 Jun	19498275
Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity.	2009 Jun 15	19362101
Pharmacological characterization of standard analgesics on mechanical allodynia in streptozotocin-induced diabetic rats.	2009 Sep	19591853
Mexiletine suppresses nodal persistent sodium currents in sensory axons of patients with neuropathic pain.	2010 May	20097124
Bisphenol A binds to the local anesthetic receptor site to block the human cardiac sodium channel.	2012	22848561
Primary erythromelalgia in a 12-year-old boy: positive response to sodium channel blockers despite negative SCN9A mutations.	2012 Sep	22170168
Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model.	2013 Dec	24052561
Bridging Functional and Structural Cardiotoxicity Assays Using Human Embryonic Stem Cell-Derived Cardiomyocytes for a More Comprehensive Risk Assessment.	2015 Nov	26259608

Patents

Sample Use Guides

In Vivo Use Guide

Mexiletine dosage must be individualized on the basis of response and tolerance. Administration with food is recommended. Initiate Mexiletine hydrochloride therapy with 200 mg every 8 hours when rapid control of arrhythmia is not essential. A minimum of two to three days between dose adjustments is recommended. The dose may be adjusted up or down in 50 or 100 mg increments. Most patients achieve satisfactory control with between 200 - 300 mg every 8 hours.The total daily dose should not exceed 400 mg.

Route of Administration: Oral

In Vitro Use Guide

HEK293 cells stably expressing human homolog of human Nav1.5 and human Nav1.7 channels were maintained under standard tissue culture conditions (5% CO2; 37°C) in Dulbecco’s modified Eagle’s medium and F-12 medium mixture at 1:1 supplemented with 10% fetal bovine serum under selection of antibiotic G418 with a concentration of 500 μg/mL. Cells were passaged every three days with 0.25% Trypsin-EDTA. Whole-cell recordings were performed 18–24 h after plating at room temperature. Whole-cell patch-clamp recordings were conducted at room temperature (22–25°C) using an EPC-10 USB amplifier. The pipette solution contained (in mM): 140 CsF, 10 NaCl, 1 EGTA, and 10 HEPES; pH 7.3 with CsOH. The bath solution for recording contained (in mM): 140 NaCl, 3 KCl, 10 HEPES, 1 MgCl2, 1 CaCl2; pH 7.3 with NaOH. Mexiletine was diluted in bath solution to the desired concentration. Bath application of 0.3 mM mexiletine resulted in a reduction of Nav1.5 or Nav1.7 currents, while V1/2 values were not significantly shifted for even up to 1.0 mM.

Name

Type

Language

MEXILETINE

Official Name

English

MEXILETINE [MI]

Common Name

English

DL-MEXILETINE

Common Name

English

(RS)-MEXILETINE

Common Name

English

1-METHYL-2-(2,6-XYLYLOXY)ETHYLAMINE

Systematic Name

English

(±)-MEXILETINE

Common Name

English

(±)-2-AMINO-1-(2',6'-DIMETHYLPHENOXY)PROPANE

Common Name

English

1-(2,6-DIMETHYLPHENOXY)-2-PROPANAMINE

Systematic Name

English

MEXILETINE [VANDF]

Common Name

English

1-(2',6'-DIMETHYLPHENOXY)-2-AMINOPROPANE

Common Name

English

Mexiletine [WHO-DD]

Common Name

English

ETHYLAMINE, 1-METHYL-2-(2,6-XYLYLOXY)-

Systematic Name

English

mexiletine [INN]

Common Name

English

2-PROPANAMINE, 1-(2,6-DIMETHYLPHENOXY)-

Systematic Name

English

(2-((2,6-DIMETHYLPHENYL)OXY)-1-METHYLETHYL)AMINE

Systematic Name

English

2-AMINO-1-(2,6-DIMETHYLPHENOXY)PROPANE

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

728219