Pharmacology · Class
Cholinesterase inhibitors !
Medicines that slow the breakdown of acetylcholine, so more of it acts on nerves and muscles. Used in myasthenia gravis, Alzheimer disease and anaesthesia.
Updated 2026-11-01
What they are
Drugs that block acetylcholinesterase, the enzyme that ends the action of acetylcholine at synapses (see the topic «Cholinergic transmission»). Quaternary drugs that stay outside the brain (neostigmine, pyridostigmine, edrophonium) act at the neuromuscular junction and autonomic synapses; drugs that enter the brain (donepezil, rivastigmine, galantamine, physostigmine) also act centrally. Organophosphate insecticides and nerve agents are irreversible inhibitors of the same enzyme and cause cholinergic poisoning.
Mechanism of action
Acetylcholinesterase normally splits acetylcholine within milliseconds. Edrophonium, donepezil and galantamine bind the enzyme reversibly without reacting; neostigmine, pyridostigmine, physostigmine and rivastigmine carbamylate its catalytic serine, which recovers slowly over hours; organophosphates phosphorylate it, a bond that becomes permanent once it «ages». Acetylcholine then builds up at muscarinic and nicotinic receptors.
Target: Acetylcholinesterase (and butyrylcholinesterase for rivastigmine)
Drugs in this class
- NeostigmineA cholinesterase inhibitor that reverses muscle relaxants after surgery and treats myasthenia gravis. It does not…Acetylcholinesterase
- PyridostigmineThe standard oral medicine for the weakness of myasthenia gravis. It lasts longer than neostigmine and causes fewer…Acetylcholinesterase
- DonepezilA once-daily cholinesterase inhibitor for Alzheimer dementia. It modestly helps memory and daily function but does not…Acetylcholinesterase
- PhysostigmineThe cholinesterase inhibitor that enters the brain, used as an antidote for severe anticholinergic delirium. It acts…Acetylcholinesterase
- EdrophoniumA very short-acting cholinesterase inhibitor once used as a bedside test for myasthenia gravis. Antibody tests have…Acetylcholinesterase
- RivastigmineA cholinesterase inhibitor for Alzheimer dementia and the dementia of Parkinson disease, given as capsules or a skin…Acetylcholinesterase and butyrylcholinesterase
- GalantamineA reversible cholinesterase inhibitor for mild to moderate Alzheimer dementia, with side effects like those of…Acetylcholinesterase
Others in the class
- Ambenonium
- Echothiophate (eye)
- Tacrine (withdrawn, liver toxicity)
Test yourself
Think of the answer, then tap the question to see it.
Why does neostigmine not cause confusion, while physostigmine can act on the brain?
Neostigmine is a charged quaternary amine that does not cross the blood-brain barrier; physostigmine is an uncharged tertiary amine that does.
A patient with myasthenia gravis on pyridostigmine becomes weak, sweaty and salivates heavily, with small pupils. What is the likely problem?
Cholinergic crisis from too much cholinesterase inhibitor: the drug is withheld, the airway is supported and atropine treats the muscarinic signs.
What does «ageing» of acetylcholinesterase mean after organophosphate poisoning?
The phosphorylated enzyme loses an alkyl group and becomes permanently resistant to reactivation by oximes such as pralidoxime, so oximes work only if given early.
Which three cholinesterase inhibitors are used for Alzheimer dementia?
Donepezil, rivastigmine and galantamine.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 12 (McGraw Hill, 2023); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 21 (McGraw Hill, 2023); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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Representative model, for educational purposes only.