Pharmacology · Cholinesterase inhibitors
Physostigmine !
The cholinesterase inhibitor that enters the brain, used as an antidote for severe anticholinergic delirium. It acts quickly but briefly.
Updated 2026-11-01
The figure shows Torpedo (electric ray) acetylcholinesterase after reaction with rivastigmine: the carbamoyl group stays bonded to the catalytic serine and the leaving phenol (NAP) remains in the gorge. Physostigmine blocks the enzyme the same way, by carbamylating that serine.
Mechanism of action
Physostigmine, an alkaloid from the Calabar bean, is a tertiary amine that crosses the blood-brain barrier. It inhibits acetylcholinesterase in the brain and the periphery, so acetylcholine rises and outcompetes drugs that block muscarinic receptors. It reverses both the central signs (delirium, agitation, hallucinations, coma) and the peripheral signs of the anticholinergic syndrome.
- Crosses the blood-brain barrier (tertiary amine)
- Carbamylates acetylcholinesterase in brain and body
- Acetylcholine rises and outcompetes the anticholinergic drug
- Delirium and peripheral signs reverse within minutes
Pharmacokinetics
- Distribution
- Enters the brain easily
- Metabolism
- Broken down quickly; the person may fall back into delirium or coma after one to two hours
- Onset and duration
- Minutes after slow intravenous injection; effect lasts about 45 to 60 minutes
Indications
- Reversal of central nervous system effects of drugs that cause the anticholinergic syndrome (atropine, scopolamine, antihistamines, some plants) Anticholinergic toxicity (incl. scopolamine «burundanga») →
Adverse effects
Common
- Nausea, vomiting and salivation
- Sweating
- Bradycardia if injected too fast
Contraindications
- Asthma
- Gangrene
- Diabetes
- Cardiovascular disease
- Mechanical obstruction of the bowel or urogenital tract, or a vagotonic state
- Use with choline esters or depolarizing muscle relaxants (succinylcholine)
Key interactions
- Succinylcholine
- Prolonged block; combination contraindicated
- Tricyclic antidepressant overdose
- Does not reverse the conduction defects and arrhythmias of tricyclics, and may add seizures
- Atropine
- Antidote for physostigmine excess; given together they cancel each other
What is monitored
- Continuous ECG and heart rate
- Mental status and seizures
- Airway, secretions and oxygen saturation
- Return of delirium after the effect wears off
Administration and safety
- Injected slowly into a vein or into a muscle; fast injection causes bradycardia, salivation and seizures
- Atropine is kept ready at the bedside
- Stopped if salivation, vomiting, urination or defecation become excessive
Nursing care
- Put the patient on a cardiac monitor before the dose
- Have suction, airway equipment and atropine ready
- Reassess mental status often: delirium can return within one to two hours
Pregnancy and breastfeeding
Safety in pregnancy has not been established; it is used when the benefit outweighs the risk in severe poisoning.
Test yourself
Think of the answer, then tap the question to see it.
Why does physostigmine, and not neostigmine, reverse anticholinergic delirium?
Physostigmine is a tertiary amine that enters the brain; neostigmine is quaternary and stays outside.
What is the antidote if physostigmine causes a cholinergic crisis?
Atropine.
Why is caution needed with physostigmine in a tricyclic antidepressant overdose?
It does not fix the cardiac conduction problems of tricyclics and can cause seizures.
Related drugs
Related conditions
← Back to the class: Cholinesterase inhibitors
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 - PHYSOSTIGMINE SALICYLATE 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).
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Representative model, for educational purposes only.