Mexiletine

Summary

Mexiletine (CHEMBL558) is an approved small-molecule anti-arrhythmia drug (ATC C01BB02) targeting SCN4A; indicated across 12 conditions including myocardial infarction and ventricular fibrillation.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C01BB02
• Targets: 1 (SCN4A)
• Indications: 12 conditions
• Clinical trials: 23
• Chemistry: 179.26 Da · C11H17NO

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL558
Name	Mexiletine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	4178
ChEBI	CHEBI:6916
ATC	C01BB02
Molecular formula	C11H17NO
Molecular weight	179.26
InChIKey	VLPIATFUUWWMKC-UHFFFAOYSA-N

SMILES: CC1=C(C(=CC=C1)C)OCC(C)N

IUPAC name: 1-(2,6-dimethylphenoxy)propan-2-amine

ChEBI definition: An aromatic ether which is 2,6-dimethylphenyl ether of 2-aminopropan-1-ol.

Pharmacological roles (ChEBI): anti-arrhythmia drug.

Also known as: (rs)-mexiletine, Dl-mexiletine, Mexiletina, Mexiletine, SID90341048, mexiletine, MEXILETINE, (R/S)-Mexiletine, Mexiletine; rac-Mexiletine

Parent form; salt/anhydrous children: CHEMBL1200606

Patent coverage: 4,057 distinct patent families (15,463 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
SCN4A	Nav1.4	Antagonist	3.4	0%	P35499

Broader ChEMBL bioactivity targets: 16 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Amine oxidase [flavin-containing] A, Sodium channel protein type 5 subunit alpha, Sodium channel alpha subunits; brain (Types I, II, III), Voltage-gated L-type calcium channel, Lysosomal acid glucosylceramidase, 5-hydroxytryptamine receptor 2A, Sodium-dependent serotonin transporter, Potassium channel subfamily K member 3, Potassium channel subfamily K member 2.

Bioactivity

ChEMBL activities: 8 potent at pChembl ≥ 5 of 25 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR2B	6.14	Ki	724	nM	CHEMBL_ACT_7749763
HTR2B	5.94	IC50	1138	nM	CHEMBL_ACT_7749762
SCN2A	5.54	IC50	2900	nM	CHEMBL_ACT_2344170
SCN5A	5.52	IC50	3000	nM	CHEMBL_ACT_23165475
KCNK2	5.39	IC50	4100	nM	CHEMBL_ACT_29291079
SCN9A	5.13	IC50	7400	nM	CHEMBL_ACT_24977324
HTR2B	5.07	AC50	8500	nM	CHEMBL_ACT_25227732
KCNH2	5	IC50	10000	nM	CHEMBL_ACT_5219025

Target pathways

Aggregated over 1 target gene(s): SCN4A.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Developmental Biology	1	SCN4A
L1CAM interactions	1	SCN4A
Muscle contraction	1	SCN4A
Axon guidance	1	SCN4A
Interaction between L1 and Ankyrins	1	SCN4A
Cardiac conduction	1	SCN4A
Phase 0 - rapid depolarisation	1	SCN4A
Nervous system development	1	SCN4A

Dominant GO biological processes

GO term	Targets
sodium ion transport	1
muscle contraction	1
sodium ion transmembrane transport	1
cardiac muscle cell action potential involved in contraction	1
regulation of skeletal muscle contraction by action potential	1
action potential	1
monoatomic ion transport	1
monoatomic ion transmembrane transport	1
transmembrane transport	1

Indications & clinical

Indications

12 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
myocardial infarction	3	MONDO:0005068	EFO:0000612
ventricular fibrillation	3	MONDO:0000190	EFO:0004287
myotonic dystrophy	3	MONDO:0016107	Orphanet:273
Charcot-Marie-Tooth disease	2	MONDO:0015626	MONDO:0015626
benign essential blepharospasm	2	MONDO:0011728	MONDO:0011728
dystonic disorder	2	MONDO:0003441	MONDO:0003441
irritable bowel syndrome	1	MONDO:0005052	EFO:0000555

5 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 23.

Phase distribution

Phase	Trials
PHASE2	8
PHASE3	7
Not specified	4
PHASE4	2
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01811355	PHASE4	COMPLETED	Mexiletine for the Treatment of Muscle Cramps in ALS
NCT02260388	PHASE4	COMPLETED	Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations
NCT00000464	PHASE3	COMPLETED	Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE)
NCT00000518	PHASE3	COMPLETED	Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM)
NCT00004647	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Mexiletine for Painful Diabetic Neuropathy
NCT02336477	PHASE3	COMPLETED	Mexiletine and Non Dystrophic Myotonias
NCT04624750	PHASE3	COMPLETED	Open Label Study in Adolescents and Children With Myotonic Disorders
NCT04700046	PHASE3	WITHDRAWN	Study to Investigate the Efficacy and Safety of Mexiletine in Patients With Myotonic Dystrophy Type 1 and Type 2
NCT05017155	PHASE3	UNKNOWN	MExiletine Versus Lamotrigine in Non-Dystrophic Myotonias
NCT00001784	PHASE2	COMPLETED	Mexiletine for the Treatment of Focal Dystonia
NCT00383682	PHASE2	COMPLETED	Efficacy of Opioids and Mexiletine for the Treatment of Postamputation Pain
NCT00832000	PHASE2	COMPLETED	Effectiveness of Mexiletine for Treating People With Non-Dystrophic Myotonia
NCT01406873	PHASE2	COMPLETED	Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type 1
NCT01849770	PHASE2	COMPLETED	Mexiletine in Sporadic Amyotrophic Lateral Sclerosis (SALS)
NCT02045667	PHASE2	COMPLETED	Combined N-of-1 Trials Mexiletine vs Placebo in Patients With Non-Dystrophic Myotonia (NDM)
NCT02561702	PHASE2	COMPLETED	Mexiletine for Muscle Cramps in Charcot Marie Tooth Disease
NCT02781454	PHASE2	COMPLETED	Mexiletine in Sporadic Amyotrophic Lateral Sclerosis
NCT01717404	PHASE1	COMPLETED	Effects of Mexiletine on Colonic Transit in a Patient With Irritable Bowel Syndrome - Constipation (IBS-C)
NCT02308748	PHASE1	COMPLETED	Ability of Late Sodium or Calcium Current Block to Balance the ECG Effects of Potassium Current Block
NCT04616807	Not specified	ACTIVE_NOT_RECRUITING	An Observational Study in Adult Patients With Non-dystrophic Myotonic Disorders
NCT04622553	Not specified	ACTIVE_NOT_RECRUITING	Open-label Extension Study in Paediatric Patients Who Have Completed the MEX-NM-301 Study.
NCT07154654	Not specified	RECRUITING	Prospective, Long Term, Observational Study (Patient Registry) of Paediatric Myotonic Disorders
NCT05619120	Not specified	UNKNOWN	The Effect of Late Na Current Blocker Mexiletine on Giant T-wave Electrical Alternans(STOP-TWA)

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 5 clinical and 9 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

25 molecules share ≥1 primary target. Top 25 by shared-target count:

Molecule	Source	Status	Shared targets
AMIODARONE	ChEMBL + PubChem	Phase 4 (approved)	SCN4A
AMITRIPTYLINE	ChEMBL + PubChem	Phase 4 (approved)	SCN4A
CARBAMAZEPINE	ChEMBL + PubChem	Phase 4 (approved)	SCN4A
CHLORPROMAZINE	ChEMBL + PubChem	Phase 4 (approved)	SCN4A
DILTIAZEM	ChEMBL + PubChem	Phase 4 (approved)	SCN4A
HALOPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	SCN4A
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN4A
LAMOTRIGINE	ChEMBL + PubChem	Phase 4 (approved)	SCN4A
LIDOCAINE	ChEMBL + PubChem	Phase 4 (approved)	SCN4A
NIFEDIPINE	ChEMBL + PubChem	Phase 4 (approved)	SCN4A
PHENYTOIN	ChEMBL + PubChem	Phase 4 (approved)	SCN4A
PIMOZIDE	ChEMBL + PubChem	Phase 4 (approved)	SCN4A
RILUZOLE	ChEMBL + PubChem	Phase 4 (approved)	SCN4A
MIBEFRADIL	ChEMBL	Phase 4 (approved)	SCN4A
SERTINDOLE	ChEMBL	Phase 4 (approved)	SCN4A
AJMALINE	ChEMBL	Phase 3	SCN4A
ELECLAZINE	ChEMBL	Phase 3	SCN4A
NITRENDIPINE	ChEMBL	Phase 3	SCN4A
TEDISAMIL	ChEMBL	Phase 3	SCN4A
TETRODOTOXIN	ChEMBL	Phase 3	SCN4A
VIXOTRIGINE	ChEMBL	Phase 3	SCN4A
CIFENLINE	ChEMBL	Phase 2	SCN4A
PF-05089771	ChEMBL	Phase 2	SCN4A
Dofetilide	PubChem	Approved	SCN4A
Ketamine	PubChem	Approved	SCN4A