AMBENONIUM

Absorption

Oral - poorly absorbed from the gastrointestinal tract.

Toxicity

LD50=150±44 mg/kg (orally in mice). Symptoms of overdose include muscle twitching, weakness and paralysis of voluntary muscles including the tongue, shoulders, neck and arms, blood pressure increase (with or without a slowing of heart rate), a sensation of internal trembling, severe anxiety, and panic. Death may occur rapidly if untreated.

Background

Ambenonium is a cholinesterase inhibitor. It is used in the management of myasthenia gravis.

Indications

Ambenonium is used to treat muscle weakness due to muscle disease (myasthenia gravis).

Definition

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

brand name

Mytelase (Sanofi Aventis).

Pharmacokinetics

Ambenonium, similar to pyridostigmine and neostigmine, is used for the treatment of muscle weakness and fatigue in people with myasthenia gravis. It is postulated to exert its therapeutic effect by enhancing cholinergic function through the inhibition of the acetylcholine hydrolysis by acetylcholinesterase. Increased levels of acetylcholine has peripheral effects, as acetylcholine is also used in the brain, where it tends to cause excitatory actions. The glands that receive impulses from the parasympathetic part of the autonomic nervous system are also stimulated in the same way. This is why an increase in acetylcholine causes a decreased heart rate and increased production of saliva. Ambenonium is used less commonly than neostigmine or pyridostigmine but may be preferred in patients hypersensitive to the bromide ion. Ambenonium produces fewer muscarinic side effects than neostigmine, but more than pyridostigmine.

Pharmacology

The pharmacological properties of ambenonium are similar to neostigmine and pyridostigmine, and it works by reversible inactivation of cholinesterase.

Synthesis

Ambenonium, [oxalyl-bis-(iminoethylen)]-bis-[ortho-(chlorobenzyl) diethylammonium] chloride (13.2.15), is made by reacting diethyloxalate with two moles of N,N-diethylethylendiamine, forming oxalyl-bis-(iminoethylen)-bis-N,N-diethylamine (13.2.14), which is alkylated by two moles of 2-chlorobenzylchloride, giving ambenonium (13.2.15) [46¨C48].

Metabolism

Plasma and hepatic