Originator
Mytelase CL,Winthrop,US,1956
Uses
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.
