Stereochemistry | RACEMIC |
Molecular Formula | C11H17NO |
Molecular Weight | 179.2588 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
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
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
Cmax
AUC
T1/2
Doses
AEs
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as victim
Tox targets
Sourcing
PubMed
Sample Use Guides
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
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.