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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 of MEXILETINE

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

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 TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
MEXITIL
Primary
MEXITIL
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
0.21 μg/mL
100 mg single, oral
MEXILETINE plasma
Homo sapiens
0.35 μg/mL
150 mg single, oral
MEXILETINE plasma
Homo sapiens
0.45 μg/mL
200 mg single, oral
MEXILETINE plasma
Homo sapiens
0.46 μg/mL
300 mg single, oral
MEXILETINE plasma
Homo sapiens
0.81 μg/mL
400 mg single, oral
MEXILETINE plasma
Homo sapiens
1.2 μg/mL
200 mg 3 times / day multiple, oral
MEXILETINE plasma
Homo sapiens
0.59 μg/mL
100 mg 3 times / day multiple, oral
MEXILETINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
2.96 μg × h/mL
100 mg single, oral
MEXILETINE plasma
Homo sapiens
5.8 μg × h/mL
150 mg single, oral
MEXILETINE plasma
Homo sapiens
7.76 μg × h/mL
200 mg single, oral
MEXILETINE plasma
Homo sapiens
6.7 μg × h/mL
300 mg single, oral
MEXILETINE plasma
Homo sapiens
8.3 μg × h/mL
400 mg single, oral
MEXILETINE plasma
Homo sapiens
22 μg × h/mL
200 mg 3 times / day multiple, oral
MEXILETINE plasma
Homo sapiens
3.7 μg × h/mL
100 mg 3 times / day multiple, oral
MEXILETINE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
9.4 h
100 mg single, oral
MEXILETINE plasma
Homo sapiens
10.8 h
150 mg single, oral
MEXILETINE plasma
Homo sapiens
11.1 h
200 mg single, oral
MEXILETINE plasma
Homo sapiens
10 h
300 mg single, oral
MEXILETINE plasma
Homo sapiens
7 h
400 mg single, oral
MEXILETINE plasma
Homo sapiens
9.9 h
200 mg 3 times / day multiple, oral
MEXILETINE plasma
Homo sapiens
14.1 h
100 mg 3 times / day multiple, oral
MEXILETINE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
40%
100 mg single, oral
MEXILETINE plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as victim

Tox targets

PubMed

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.