1-(2,6-Dimethylphenoxy)-2-propanamine Chemical Properties

Melting point:

203-205 °C

Boiling point:

271.5±28.0 °C(Predicted)

Density 

0.979±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

ethanol: 50 mg/mL

pka

pKa 9.14± 0.01(H2O,t =25±0.2,I=0.01(NaCl))(Approximate)

form 

powder

color 

white

BCS Class

1

CAS DataBase Reference

31828-71-4(CAS DataBase Reference)

NIST Chemistry Reference

Mexiletine(31828-71-4)

Safety Information

Hazard Codes 

Xn

Risk Statements 

20/21/22

Safety Statements 

36

RIDADR 

3249

WGK Germany 

3

RTECS 

KR9300000

HazardClass 

6.1(b)

PackingGroup 

III

1-(2,6-Dimethylphenoxy)-2-propanamine Usage And Synthesis

Description

Mexiletine is effective both parenterally and orally , . Because the substance has a large distribution volume, a high initial dose is necessary.

Originator

Mexitil,Boehringer Ingelheim,US,1976

Uses

Cardiac depressant (anti-arrhythmic).

Uses

Mexiletine is used for ventricular extrasystole and ventricular tachycardia, and ventricular fibrillation (including during the severe period of myocardial infarction).

Uses

Mexiletine is a useful analgesia.It is used in treatment of amyotrophic lateral sclerosis comprising administering a bile acid and a phenylbutyrate compound and an additional therapeutic agent.

Definition

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

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

Clinical Use

Mexiletine (Mexitil) is an antiarrhythmic agent with pharmacological and antiarrhythmic properties similar to those of lidocaine and tocainide. Like tocainide,mexiletine is available for oral administration.
Mexiletine is useful as an antiarrhythmic agent in the management of patients with either acute or chronic ventricular arrhythmias.While it is not at present an indication for use, there is interest in using mexiletine to treat the congenital long QT syndrome when an abnormality in the SCN5A gene (LQTS 3) has been found.

Side effects

A very narrow therapeutic window limits mexiletine use. The first signs of toxicity manifest as fine tremor of the hands, followed by dizziness and blurred vision. Hypotension, sinus bradycardia, and widening of the QRS complex have been noted as the most common unwanted cardiovascular effects of IV mexiletine. The side effects of oral maintenance therapy include reversible upper gastrointestinal distress, tremor, lightheadedness, and coordination difficulties. These effects generally are not serious and can be reduced by downward dose adjustment or administering the drug with meals. Cardiovascular adverse effects, which are less common, include palpitations, chest pain, and angina or anginalike pain.

Synthesis

Mexiletine is 1-methyl-2-(2,2-dimethylphenoxy)ethylamine (18.1.11). Mexiletine is synthesized by reacting the sodium salt of 2,6-dimethylphenol with chloroacetone, forming 1-(2,6-dimethylphenoxy)-2-propanone (18.1.9). Reacting this with hydroxylamine gives the corresponding oxime (18.1.10). Reduction of the oximine group using hydrogen over Raney nickel gives mexiletine (18.1.11).

Drug interactions

An upward adjustment in dose may be required when mexiletine is administered with phenytoin or rifampin, since these drugs stimulate the hepatic metabolism of mexiletine, reducing its plasma concentration.

Precautions

Mexiletine is contraindicated in the presence of cardiogenic shock or preexisting second- or third-degree heart block in the absence of a cardiac pacemaker. Caution must be exercised in administration of the drug to patients with sinus node dysfunction or disturbances of intraventricular conduction.

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