Pharmacology · Cholinesterase inhibitors
Neostigmine !
A cholinesterase inhibitor that reverses muscle relaxants after surgery and treats myasthenia gravis. It does not enter the brain.
Updated 2026-11-01
No crystal structure of neostigmine bound to acetylcholinesterase exists. The figure shows edrophonium, a close chemical relative with the same charged trimethylammonium head, in the active site of Torpedo (electric ray) acetylcholinesterase, which shares the human enzyme's gorge and catalytic serine.
Mechanism of action
Neostigmine carbamylates the catalytic serine of acetylcholinesterase, so the enzyme stops breaking down acetylcholine for a while. More acetylcholine at the neuromuscular junction competes with non-depolarizing muscle relaxants and restores muscle strength; it also stimulates muscarinic receptors (slow heart rate, secretions, gut movement). As a charged quaternary amine it does not cross the blood-brain barrier.
- Carbamylates the serine in the active site of acetylcholinesterase
- Acetylcholine is not broken down and builds up
- It outcompetes the muscle relaxant at nicotinic receptors
- Muscle strength returns; muscarinic effects also rise
Pharmacokinetics
- Absorption
- Given intravenously for reversal; oral forms are poorly absorbed
- Distribution
- Does not cross the blood-brain barrier; about 15 to 25% bound to albumin
- Metabolism
- By liver microsomal enzymes
- Elimination
- Half-life is longer in people without kidney function
- Half-life
- Reported between about 24 and 113 minutes after intravenous injection
Indications
- Reversal of non-depolarizing neuromuscular blocking agents after surgery
- Myasthenia gravis Myasthenia gravis →
- Postoperative ileus and atony of the bladder without obstruction (older use) Postoperative ileus →
Adverse effects
Common
- Bradycardia
- Nausea, vomiting, cramps and diarrhoea
- More saliva and bronchial secretions
- Sweating, muscle twitching (fasciculations)
Contraindications
- Known hypersensitivity to neostigmine
- Peritonitis
- Mechanical obstruction of the bowel or urinary tract
Key interactions
- Atropine or glycopyrronium
- Given before or with neostigmine to block bradycardia and secretions
- Succinylcholine
- Its block is prolonged, not reversed
- Drugs that change liver drug-metabolizing enzymes
- Not studied; used with caution, since neostigmine is metabolized by liver microsomal enzymes
What is monitored
- Train-of-four response with a peripheral nerve stimulator
- Heart rate, rhythm and blood pressure
- Breathing and oxygen saturation after extubation
Administration and safety
- Given intravenously; the anticholinergic goes in a separate syringe, before neostigmine if the heart rate is already slow
- Atropine and drugs for anaphylaxis are kept at hand
- Large doses when the block has almost worn off can cause weakness of their own
Nursing care
- Check heart rate and rhythm before and after the dose
- Watch for wheeze, secretions and breathing effort in the recovery room
- Know the signs of cholinergic crisis: weakness with sweating, salivation and small pupils
- In myasthenia gravis, record strength, swallowing and breathing at regular times
Pregnancy and breastfeeding
Human data are limited; near term, cholinesterase inhibitors may irritate the uterus and trigger early labour.
Test yourself
Think of the answer, then tap the question to see it.
Why is atropine or glycopyrronium given with neostigmine at the end of surgery?
To block the muscarinic effects of the extra acetylcholine, mainly bradycardia and secretions, while the nicotinic effect reverses the muscle relaxant.
Which kind of neuromuscular block can neostigmine reverse?
Non-depolarizing block (for example rocuronium). It prolongs depolarizing block by succinylcholine.
Which two conditions are contraindications to neostigmine?
Mechanical obstruction of the bowel or urinary tract, and peritonitis.
Related drugs
Related conditions
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - NEOSTIGMINE METHYLSULFATE injection (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 12 (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.