ambenonium chloride

Originator

Mytelase CL,Winthrop,US,1956

The Uses of ambenonium chloride

Ambenonium Dichloride used in the discovery and design of ApoE4 (apolipoprotein E4) inhibitors with biological activity showing against Alzheimer’s disease. Cholinesterase inhibitor.

Definition

ChEBI: A symmetrical oxalamide-based bis-quaternary ammonium salt having ethyl and 2-chlorobenzyl groups attached to the nitrogens.

Manufacturing Process

N,N'-Bis(2-Diethylaminoethyl)Oxamide: A solution of 150 grams (1.32 mol) of 2-diethylaminoethylamine in 250 ml of xylene was gradually added to a solution of 73.0 grams (0.5 mol) of ethyl oxalate in 250 ml of xylene, with external cooling. The mixture was then refluxed for eight hours, cooled and diluted with ether. The ether-xylene solution was extracted with 10% hydrochloric acid, and the hydrochloric acid extracts were in turn extracted with ether and then made alkaline with 35% sodium hydroxide solution. The organic material which separated was extracted with ether, and the ether solution was dried over anhydrous sodium sulfate and concentrated, giving 106.5 grams of N,N'-bis(2-diethylaminoethyl)oxamide, MP 40-42°C.
N,N'-Bis(2-Diethylaminoethyl)Oxamide Bis(2-Chlorobenzochloride): A solution of 7 grams (0.025 mol) of N,N'-bis(2-diethylaminoethyl)oxamide and 16.1 grams (0.1 mol) of 2-chlorobenzyl chloride in 100 ml of acetonitrile was refluxed for eleven hours. The solid which separated upon cooling was collected by filtration and recrystallized by dissolving it in ethanol and adding ether to cause the product to separate. After drying at about 60°C (1-3 mm) there was obtained 4.1 grams of N,N'-bis(2-diethylaminoethyl)oxamide bis(2- chlorobenzochloride), MP 196-199°C.

brand name

Mytelase (Sanofi Aventis).

Therapeutic Function

Cholinesterase inhibitor

General Description

Ambenonium chloride, [oxalylbis(iminoethylene)]bis[(o-chlorobenzyl)diethylammonium]dichloride (Mytelase chloride), is a white, odorlesspowder, soluble in water and alcohol, slightly soluble inchloroform, and practically insoluble in ether and acetone.Ambenonium chloride is used for the treatment of myastheniagravis in patients who do not respond satisfactorily toneostigmine or pyridostigmine.
This drug acts by suppressing the activity of AChE. Itpossesses a relatively prolonged duration of action andcauses fewer side effects in the GI tract than the other anticholinesteraseagents. The dosage requirements vary considerably,and the dosage must be individualized accordingto the response and tolerance of the patient. Because of itsquaternary ammonium structure, ambenonium chloride isabsorbed poorly from the GI tract. In moderate doses, thedrug does not cross the blood-brain barrier. Ambenoniumchloride is not hydrolyzed by cholinesterases.

Storage

Store at RT