indication

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

pharmacology

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.

mechanism of action

Ambenonium exerts its actions against myasthenia gravis by competitive, reversible inhibition of acetylcholinesterase. The disease myasthenia gravis occurs when the body inappropriately produces antibodies against acetylcholine receptors, and thus inhibits proper acetylcholine signal transmission (when acetylcholine binds to acetylcholine receptors of striated muscle fibers, it stimulates those fibers to contract). Ambenonium reversibly binds acetylcholinesterase at the anionic site, which results in the blockage of the site of acetycholine binding, thereby inhibiting acetylcholine hydrolysis and enhancing cholinergic function through the accumulation of acetycholine at cholinergic synpases. In turn this facilitates transmission of impulses across the myoneural junction and effectively treats the disease.

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.

biotransformation

Plasma and hepatic

absorption

Oral - poorly absorbed from the gastrointestinal tract.

drug interactions

Betamethasone: The corticosteroid, betamethasone, may decrease the effect of the anticholinesterase, ambenonium.

Dexamethasone: The corticosteroid, dexamethasone, may decrease the effect of the anticholinesterase, ambenonium.

Fludrocortisone: The corticosteroid, fludrocortisone, may decrease the effect of the anticholinesterase, ambenonium.

Hydrocortisone: The corticosteroid, hydrocortisone, may decrease the effect of the anticholinesterase, ambenonium.

Prednisolone: The corticosteroid, prednisolone, may decrease the effect of the anticholinesterase, ambenonium.

Prednisone: The corticosteroid, prednisone, may decrease the effect of the anticholinesterase, ambenonium.

Tacrine: The acetylcholinesterase inhibitor, Tacrine, may increase the adverse/toxic effects of Ambenonium, a cholinergic agonist. Monitor for increased cholinergic effects and toxicity.

Triamcinolone: The corticosteroid, triamcinolone, may decrease the effect of the anticholinesterase, ambenonium.