Mexiletine is an orally effective antiarrhythmic agent noted for its benefits in treating myotonia and neuropathic pain. It operates by inhibiting sodium channels, with an IC50 of 75±8 μM for tonic block and 23.6±2.8 μM for use-dependent block, making it relevant for both cardiovascular and neurological research[1].[2].[3].[4].[5].
体内研究
Additionally, Mexiletine (30, 100 mg/kg, p.o., acutely administered) effectively counteracts mechanical allodynia and cold hyperalgesia in rats induced with Oxaliplatin[4].
体外研究
Mexiletine (10µM, 48 h) enhances both peak INa and late INa in HEK293A cells transfected with SCN5A-WT or SCN5A-1795insD, while a shorter exposure (10µM, 5 min) inhibits the late INa[3].
Mexiletine HCl/盐酸美西律 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Casq2−/− myocytes
100 μM
10 min
Mexiletine had no significant effects on Ca2+ wave parameters at the highest concentration tested (100 μM)
J Mol Cell Cardiol. 2011 Nov;51(5):760-8
Mouse cardiomyocytes
100–1,000 µM
3 minutes
Evaluate the inhibitory effect of JME-173 on L-type Ca++ currents, finding it was 12-fold more potent than Mexiletine
Front Pharmacol. 2020 Jul 30;11:1159
GH3 cells
0.28 mM
Evaluate the blocking effect of JME-173 on Na+ channels, finding its potency to block Na+ currents was 653-fold lower than Mexiletine
Front Pharmacol. 2020 Jul 30;11:1159
Casq2−/− cardiomyocytes
6 μmol/L
30 minutes
Mexiletine had no significant effect on isoproterenol-induced spontaneous Ca2+ waves
To evaluate the effect of Mexiletine on the excitability of ClCadr muscle fibers. At 10 and 25 μM, most fibers remained hyperexcitable; at 50 μM, there was a wide range in excitability; and at 100 μM, almost all fibers were hypoexcitable.
Ann Neurol. 2015 Feb;77(2):320-32
ADR mouse skeletal muscle fibers
30 μM
30 minutes
To evaluate the antimyotonic effects of Mexiletine on sarcolemma excitability in ADR mouse skeletal muscle fibers. Mexiletine at 30 μM reduced the number of action potentials, with effects comparable to 10 μM sa finamide.
Neurotherapeutics. 2024 Oct;21(6):e00455
ADR mouse skeletal muscle fibers
10 μM
30 minutes
To evaluate the antimyotonic effects of Mexiletine on sarcolemma excitability in ADR mouse skeletal muscle fibers. Mexiletine at 10 μM reduced the number of action potentials by 24.4%.
Neurotherapeutics. 2024 Oct;21(6):e00455
Rat tracheal rings
10–100 µM
15 minutes
Assess the inhibitory effect of JME-173 on carbachol-induced tracheal contraction, finding JME-173 was 15-fold more potent than Mexiletine
Front Pharmacol. 2020 Jul 30;11:1159
Mexiletine HCl/盐酸美西律 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
Cisplatin or oxaliplatin-induced neuropathy model
Intraperitoneal injection
10 mg/kg
Single dose, assessed 1 hour after administration
To evaluate the analgesic effects of mexiletine on cisplatin or oxaliplatin-induced neuropathy, results showed mexiletine was ineffective in both models
Neuro Oncol. 2014 Oct;16(10):1324-32
Mice
TGM(NS31)L12 transgenic mice
Intraperitoneal injection
25 mg/kg
Twice daily for 14 days
To evaluate the effect of mexiletine on arrhythmias, results showed that mexiletine significantly suppressed spontaneous VT/VF in transgenic mice
Cardiovasc Res. 2004 Feb 1;61(2):256-67
Mice
Mouse model of myotonia congenita
Intraperitoneal injection
5, 10, 20, 40 mg/kg
Single injection, effects evaluated at 5 to 15 minutes
To evaluate the effect of Mexiletine on motor function in a mouse model of myotonia congenita. Mexiletine at 20 mg/kg significantly improved motor function, but at 40 mg/kg, mild ataxia was observed.
Ann Neurol. 2015 Feb;77(2):320-32
ADR mice
Myotonia model
Intraperitoneal injection
10 mg/kg
Single administration, effects measured over 120 minutes
To evaluate the in vivo antimyotonic effects of Mexiletine in ADR mice. Mexiletine at 10 mg/kg significantly reduced TRR, but was less potent than sa finamide.
Neurotherapeutics. 2024 Oct;21(6):e00455
Mice
AMPA-induced lethality model
Subcutaneous injection
24.5 – 81.5 mg/kg s.c.
Single dose
Mexiletine partially protected mice against AMPA-induced lethality with a maximum effect of 30-60%.
Br J Pharmacol. 2001 Jul;133(6):789-96
Mice
Trpm4 knockout mice
Langendorff perfusion
40 µg/mL
Single dose, 20 minutes duration
To study the effect of Mexiletine on cardiac electrical activity in Trpm4?/? mice, results showed that Trpm4?/? hearts were more sensitive to Mexiletine with more pronounced QRS broadening.
Netherlands
... 展开 >> Departments of Neurology, Radboud University Nijmegen Medical Centre, the Netherlands
Nijmegen, Gelderland, Netherlands, 6500HB 收起 <<
Mexiletine HCl/盐酸美西律 实验方案
计算器
存储液制备
1mg
5mg
10mg
1 mM
5 mM
10 mM
4.64mL
0.93mL
0.46mL
23.18mL
4.64mL
2.32mL
46.36mL
9.27mL
4.64mL
Mexiletine HCl/盐酸美西律 技术信息
CAS号
5370-01-4
分子式
C11H18ClNO
分子量
215.72
SMILES Code
CC(N)COC1=C(C)C=CC=C1C.[H]Cl
MDL No.
MFCD00216024
别名
KOE-1173 hydrochloride; Mexiletine(hydrochloride); Ko 1173; Mexiletine hydrochloride
Netherlands
... 展开 >> Departments of Neurology, Radboud University Nijmegen Medical Centre, the Netherlands
Nijmegen, Gelderland, Netherlands, 6500HB 收起 <<
United States, California
... 展开 >>
UCLA, Neuromuscular Research Center
Los Angeles, California, United States, 90095
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
University of Massachusetts (Worcester) Memorial Medical Center
Worcester, Massachusetts, United States, 01655
United States, Missouri
Washington University Medical School
Saint Louis, Missouri, United States, 63110
United States, New York
SUNY Upstate Medical Center
Syracuse, New York, United States, 13210
United States, Pennsylvania
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390-8897
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195 收起 <<
United States, Arizona
... 展开 >>
Barrow Neurological Institute
Phoenix, Arizona, United States, 85013
United States, California
University of California, Irvine
Orange, California, United States, 92868
United States, Georgia
Augusta University
Augusta, Georgia, United States, 30912
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, New York
Columbia Universtiy Medical Center
New York, New York, United States, 10032
United States, Pennsylvania
Pennsylvania State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Washington
University of Washington
Seattle, Washington, United States, 98195 收起 <<
搜索
