normethadone

Toxicity

The toxic effects of normethadone are similar to those of other opioids. It can produce respiratory depression, depression of central nervous system function, and constipation .

Originator

Normethadone, Isotec, Inc.

Definition

ChEBI: Normethadone is a diarylmethane.

Indications

For use in the treatment of cough when other less potent treatments have failed .

Background

Normethadone is used as an opioid antitussive in combination with Oxilofrine. It is marketed in Canada by Valeant under the tradename Cophylac.

Manufacturing Process

65 g of thin powder sodium amide was added to a solution of 289 g diphenylacetonitrile in 300 ml benzene for 15-20 minutes at temperature 45°50°C. Then the mixture was cooled to about 25°C, 182 g 2dimethyaminoethylchloride was added dropwise. On ending the reaction it was heated to reflux for 15 minutes, diluted with water, the benzene layer separated and washed with diluted hydrochloric acid. The acid layer was alkalified with sodium hydroxide, extracted with ether and dried over potash. The ether was distilled off to dryness and the residue solidified to give colorless crystals of 4-dimethylamino-2,2-diphenylbutyronitrile. The C2H5MgBr was made from 66.5 g of magnesium, 300 ml dry ether and 33 g ethyl bromide and mixed with above prepared nitrile in 150 ml toluene. After the ending of reaction, the mixture was heated for 1.5 hour on the steam bath to give hard-grained bulk. It was mixed with 600 ml concentrate hydrochloric acid in 1500 ml water. On cooling 500 ml benzene was added and three layers arose. The middle layer crystallized shortly. The crystals were filtered off, washed with 100 ml 2 N hydrochloric acid and 3 x 100 ml acetone. 6Dimethylamino-4,4-diphenyl-3-hexanone was prepared as a hydrochloride. MP: 231°C. The salt may be transformed into the base by adding of an equivalent of any basic compound (triethyl amine, soda and so on).

Therapeutic Function

Narcotic analgesic, Antitussive

Pharmacokinetics

Normethadone is an opioid which suppresses coughing by central and peripheral mechanisms .

Metabolism

Not Available