Ambenonium is a synthetic reversible cholinesterase inhibitor used primarily in the management of myasthenia gravis, a chronic autoimmune disorder characterized by weakness and rapid fatigue of skeletal muscles. By inhibiting acetylcholinesterase, ambenonium increases the levels of acetylcholine at the neuromuscular junction, enhancing neuromuscular transmission and improving muscle strength. The drug was developed in the mid-20th century as part of efforts to find safer and more effective alternatives to earlier cholinesterase inhibitors such as neostigmine and pyridostigmine. Its oral activity and relatively long duration of action made it a useful option for long-term symptomatic management of myasthenia gravis. Over time, ambenonium has been widely used in clinical practice, particularly in patients who require consistent control of muscle weakness, and it remains an important therapeutic agent in the treatment of this neuromuscular condition.
BRAND NAMES
The primary brand name for ambenonium is Mytelase. In some regions, it may also be marketed under other less common names, but Mytelase is the most widely recognized and used internationally for the treatment of myasthenia gravis.
MECHANISM OF ACTION
Ambenonium works by reversibly and competitively inhibiting acetylcholinesterase (AChE), the enzyme responsible for breaking down the neurotransmitter acetylcholine (ACh) at nerve synapses, particularly at the neuromuscular junction (NMJ). By blocking AChE, it prevents the breakdown of acetylcholine, increasing its concentration and prolonging its action. This enhances cholinergic signaling, thereby improving muscle contraction and strength, which is especially beneficial in conditions such as myasthenia gravis.
PHARMACOKINETICS
Absorption
Ambenonium is poorly absorbed when taken orally, mainly because it is a quaternary ammonium compound that remains ionized at physiological pH. Its absorption is also notably influenced by the presence of food.
Distribution
The steady-state volume of distribution of ambenonium has been reported in rat studies to be approximately 0.20 to 0.31 L/kg, indicating that it is a drug with a relatively low volume of distribution.
Metabolism
Ambenonium undergoes minimal metabolism in the body. It is largely excreted unchanged in the urine, with only a small portion metabolized by the liver. Because of its quaternary ammonium structure, it is resistant to extensive hepatic biotransformation, which contributes to its predictable pharmacokinetic profile and duration of action.
Excretion
Ambenonium is primarily eliminated unchanged in the urine, with only a small fraction undergoing hepatic metabolism. Its renal excretion is the main route of removal from the body, making kidney function an important factor in determining drug clearance and dosing.
PHARMACODYNAMICS
Ambenonium is a reversible, competitive acetylcholinesterase inhibitor that enhances cholinergic neurotransmission at the neuromuscular junction. By inhibiting acetylcholinesterase, it prevents the breakdown of acetylcholine, increasing its concentration and prolonging its action. This results in improved muscle contraction and strength, making it effective in managing myasthenia gravis and other conditions characterized by skeletal muscle weakness. Its effects are dose-dependent and generally correlate with plasma drug concentrations, providing predictable symptomatic relief.
DOSAGE AND ADMINISTRATION
Route: Oral
Starting dose: 2 mg, 2–3 times daily
Maintenance dose: Gradually adjusted based on response, usually up to 20 mg/day divided into multiple doses
Administration: Can be taken with or without food, but should be taken at the same time each day for consistency.
DRUG INTERACTIONS
Ambenonium (Mytelase) can interact with medications that affect acetylcholine, potentially leading to increased muscle weakness or bradycardia. These include beta-blockers, certain antibiotics, anesthetics, and ganglionic blockers such as mecamylamine. Concurrent use with prednisolone may initially worsen muscle weakness, necessitating close monitoring. It should also be avoided with other cholinergic drugs like atropine, as they can mask serious symptoms.
FOOD INTERACTIONS
Ambenonium’s absorption can be affected by food intake. While it can be taken with or without food, consuming it with food may slightly alter its bioavailability. For consistent therapeutic effects, it is recommended to take the medication at the same times and under similar conditions (with or without meals) each day. No specific foods are strictly contraindicated, but maintaining a consistent routine helps ensure predictable drug action.
CONTRAINDICATIONS
Ambenonium (Mytelase) is contraindicated in patients with a known hypersensitivity to the drug, in individuals with mechanical obstruction of the gastrointestinal or urinary tracts, and in those taking certain interacting medications.
SIDE EFFECTS
Common Side Effects:
Gastrointestinal issues: Nausea, vomiting, diarrhea, abdominal cramps, and stomach pain.
Increased secretions: Excessive salivation (drooling), watery eyes (lachrymation), increased bronchial secretions, and sweating.
Urinary issues: Urinary urgency and frequent urination (pollakiuria).
Vision changes: Constricted pupils (miosis) and blurred vision.
Neuromuscular effects: Muscle cramps, muscle twitching (fasciculation), and sometimes generalized malaise.
Other: Dizziness, a spinning sensation (vertigo), headache, and anxiety.
OVERDOSE
Muscarinic effects: Excess salivation, sweating, nausea, vomiting, diarrhea, abdominal cramps, and blurred vision
Nicotinic effects: Muscle twitching, weakness, and cramps
Cardiovascular: Bradycardia (slow heart rate), hypotension
Respiratory: Difficulty breathing, respiratory muscle weakness
TOXICITY
Ambenonium is a strong cholinesterase inhibitor with a narrow therapeutic window, meaning the difference between an effective and toxic dose is small. Toxicity essentially represents an exaggerated pharmacological effect, resulting in a cholinergic crisis caused by overstimulation of muscarinic and nicotinic receptors throughout the body.
