Mexiletine hydrochloride Chemical Properties

Melting point:

200-203°C

Density 

1.12 g/cm3

storage temp. 

2-8°C

solubility 

ethanol: 50 mg/mL

pka

9.0(at 25℃)

form 

powder

color 

white

λmax

272nm(MeOH)(lit.)

Merck 

14,6169

Stability:

Hygroscopic

CAS DataBase Reference

5370-01-4(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xn

Risk Statements 

20/21/22-36/37/38-22

Safety Statements 

36-26

WGK Germany 

3

RTECS 

KR9300000

HS Code 

2922190900

Toxicity

LD50 in male, female rats, mice, rabbits (mg/kg): 350, 400, 310, 400, 180, 160 orally; in male, female rats, mice (mg/kg): 27, 30, 43, 50 i.v. (Kast)

MSDS

• Language:English Provider:SigmaAldrich

Mexiletine hydrochloride Usage And Synthesis

Description

Mexiletine is a voltage-gated sodium channel blocker and class Ib antiarrhythmic agent that preferentially binds to open/inactive channels. It inhibits aconitine-induced dysrhythmias in mice with ED₅₀ values of 57 and 107 mg/kg for intraperitoneal and oral administration, respectively. Mexiletine decreases or inhibits conduction across the Purkinje fiber-muscle junction, shortens action potential duration, and decreases the refractory period when used at concentrations less than 5 μg/ml in isolated canine Purkinje fiber and ventricular muscle preparations.

Chemical Properties

White to Off-White Solid

Originator

Mexitil,Boehringer Ingelheim,US,1976

Uses

Antiarrhythmic (class IB)

Uses

antipsychotic

Uses

Mexiletine hydrochloride has been used as a sodium channel blocker:

• expressed in chinese hamster ovary cells
• in human embryonic kidney (HEK) cells for whole cell patch-clamp studies
• electrophysiology studies in HEK cells expressing Nav1.7 protein

Definition

ChEBI: A hydrochloride composed of equimolar amounts of mexiletine and hydrogen chloride.

Manufacturing Process

The sodium salt of dimethyl phenol was reacted with chloroacetone and this product with hydroxylamine to give the starting material.
245 g of this 1-(2',6'-dimethyl-phenoxy)-propanone-(2)-oxime were dissolved in 1,300 cc of methanol, and the solution was hydrogenated at 5 atmospheres gauge and 60°C in the presence of Raney nickel. After the calculated amount of hydrogen had been absorbed, the catalyst was filtered off, the methanol was distilled out of the filtrate,and the residue, raw 1-(2',6'-dimethylphenoxy)-2-amino-propane, was dissolved in ethanol. The resulting solution was acidified with ethereal hydrochloric acid, the acidic solution was allowed to cool, and the precipitate formed thereby was collected by vacuum filtration. The filter cake was dissolved in ethanol and recystallized therefrom by addition of ether. 140.5 g (51.5% of theory) of a substance having a melting point of 203°C to 205°C were obtained, which was identified to be 1-(2',6'- dimethyl-phenoxy)-2-anino-propane hydrochloride.

brand name

Mexitil (Boehringer Ingelheim).

Therapeutic Function

Antiarrhythmic

General Description

Mexiletine hydrochloride,1-methyl-2-(2,6-xylyloxy)ethylamine hydrochloride (Mexitil)(pKa 8.4), is a class IB antiarrhythmic agent that is effectivewhen given either intravenously or orally. It resembles lidocainein possessing a xylyl moiety but otherwise is differentchemically. Mexiletine hydrochloride is an ether and is notsubject to the hydrolysis common to the amides lidocaineand tocainide. Its mean half-life on oral administration isapproximately 10 hours.
Although not subject to hydrolysis, mexiletine hydrochlorideis metabolized by oxidative and reductiveprocesses in the liver. Its metabolites, p-hydroxymexiletineand hydroxymethylmexiletine, are not pharmacologicallyactive as antiarrhythmic agents.

Biological Activity

Use-dependent sodium channel blocker (IC 50 values are 75.3 and 23.6 μ M for tonic and use-dependent block respectively). Class Ib antiarrhythmic, neuroprotective and antimyotonic agent.

Biochem/physiol Actions

Mexiletine is a potent sodium channel blocker. It is a cardiac antiarrhythmic and is used as an adjuvant in headache and neuropathic pain Mexiletine is used for treating myotonia in sodium channelopathies and reduces the cardiac action potential depolarization but shows no impact on atrial refractoriness. Its inhibitory effect on sodium channels is effective in treating potassium aggravated myotonia.

Clinical Use

Mexiletine hydrochloride, like class I antiarrhythmicagents, blocks the fast Na channel in cardiac cells. It isespecially effective on the Purkinje fibers in the heart. Thedrug increases the threshold of excitability of myocardialcells by reducing the rate of rise and amplitude of the actionpotential and decreases automaticity.
Mexiletine hydrochloride is used for long-term oral prophylaxisof ventricular tachycardia. The drug is given in200- to 400-mg doses every 8 hours.

storage

Desiccate at +4°C

Mexiletine hydrochloride (5370-01-4)Related Product Information

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