Neostigmine
Neostigmine metilsulfate
Also known as: Prostigmin · Robinul-Neostigmine · Neostigmine metilsulfate · Neostigmine bromide
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Audited v13 dosing evidence
Reviewed non-calculator evidenceReviewed non-calculator evidence (1)
Evidence only — not for automatic calculation
Crocodiles/gallamine reversal; may cause emesis and lacrimation; fast 24–48 hr before use; effects enhanced if combined with 75 mg hyaluronidase per dose when administered SC, IM188
TABLE 127.5. Agent: Neostigmine. Dosage: 0.03–0.25 mg/kg IM188 0.063 mg/kg IV188 0.07–0.14 mg/kg IM235. Species/Comments: Crocodiles/gallamine reversal; may cause emesis and lacrimation; fast 24–48 hr before use; effects enhanced if combined with 75 mg hyaluronidase per dose when administered SC, IM188.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Neostigmine is a reversible acetylcholinesterase inhibitor used primarily in veterinary medicine for the diagnosis and management of myasthenia gravis, as well as to antagonize the effects of non-depolarizing neuromuscular blocking agents. Because of its polar structure, it has poor penetration into the central nervous system (CNS).
CLINICAL WARNING: Administration can precipitate a life-threatening cholinergic crisis. It is highly recommended to use a combined formulation with glycopyrronium or have atropine drawn up and ready for immediate intravenous administration to control severe muscarinic side effects (e.g., severe bradycardia, asystole, bronchoconstriction).
Clinical Pearl: Compared to edrophonium (Tensilon), neostigmine has a slower onset of action but a significantly longer duration of effect (30 minutes to 2 hours), making it useful for diagnostic exercise testing in dogs with brief collapse episodes.
Mechanism of action
Neostigmine acts as a reversible inhibitor of the enzyme acetylcholinesterase at the neuromuscular junction (NMJ) and autonomic synapses.
Inhibition of acetylcholinesterase → Decreased breakdown of acetylcholine (ACh) → Accumulation of ACh in the synaptic cleft → Prolonged and enhanced stimulation of nicotinic and muscarinic receptors → Improved muscle contraction (in myasthenia gravis) and reversal of non-depolarizing neuromuscular blockade.
Safety & warnings
Contraindications
- Mechanical gastrointestinal obstruction
- Mechanical urinary tract obstruction
- Peritonitis
Adverse effects
- Nausea and vomiting
- Increased salivation (ptyalism)
- Diarrhoea
- Muscle fasciculations and cramps
- Weakness and paralysis (with overdose)
- Severe bradyarrhythmias or asystole
- Miosis and nystagmus
- Hypotension
- Bronchoconstriction and increased bronchial secretions
Precautions
Use with extreme caution in patients with:
- Bronchial disease (especially feline asthma)
- Bradycardia and other arrhythmias
- Hypotension
- Renal impairment
- Epilepsy
Always have atropine (0.05 mg/kg IV) available for immediate administration when using neostigmine to diagnose myasthenia gravis.
Drug interactions
May antagonize the neuromuscular effects of neostigmine
May antagonize the neuromuscular effects of neostigmine
May antagonize the neuromuscular effects of neostigmine
May increase clinical severity of myasthenia gravis and reduce neostigmine effectiveness
May reduce effectiveness in myasthenia gravis; concurrent use may result in severe bradycardia
Neostigmine inhibits its metabolism, prolonging and enhancing its clinical effect (combined use not recommended)
Neostigmine antagonizes their effect (therapeutic use)
Antagonizes the muscarinic effects of neostigmine (used therapeutically to manage side effects)
Monitoring
- Heart rate and rhythm (ECG monitoring recommended during IV administration)
- Respiratory rate, effort, and airway patency
- Signs of cholinergic crisis (excessive salivation, urination, defecation, miosis)
- Muscle strength and fasciculations
Pharmacokinetics
Absorption
Poorly absorbed orally. Low CNS penetration due to its polar structure.
Distribution
Does not readily cross the blood-brain barrier.
Metabolism
Metabolized by cholinesterases at the neuromuscular junction and in the liver.
Elimination
Excreted primarily in the urine.
Overdose
Cholinergic Crisis can occur with overdosage, presenting with both muscarinic and nicotinic effects (SLUDGE signs: Salivation, Lacrimation, Urination, Defecation, Gastrointestinal distress, Emesis), miosis, bradycardia, hypotension, muscle cramps, fasciculations, weakness, paralysis, bronchoconstriction, ataxia, seizures, and coma.
Management:
- Maintenance of respiration is the absolute priority.
- Administer Atropine to control muscarinic signs (note: atropine does not antagonize nicotinic effects like muscle weakness and paralysis).
- If muscle twitching is severe, control with small doses of a competitive neuromuscular blocker.
- The cholinesterase reactivator pralidoxime can be used as an adjunct to atropine.
- Provide intensive supportive care as required.
Available products
Formulations
- Injectable: 2.5 mg/ml solution
- Injectable: Glycopyrronium bromide 0.5 mg/ml and neostigmine metilsulfate 2.5 mg/ml solution
- Oral: 15 mg tablets
Veterinary
- Neostigmine 2.5 mg/ml injection (special order)
- Glycopyrronium bromide 0.5 mg/ml / Neostigmine metilsulfate 2.5 mg/ml injection
Human-labeled
- Neostigmine 15 mg tablets
Regulatory status
Available as POM (Prescription Only Medicine)
Available as POM-V. Injectable often requires special order.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store at room temperature. Protect from light. Keep out of reach of children.
Client information
This medication is used to help diagnose or treat a condition called myasthenia gravis (a disease causing severe muscle weakness), or to reverse certain muscle relaxants used during anesthesia.
- Watch closely for side effects: If your pet begins drooling excessively, vomiting, having diarrhea, or showing signs of breathing difficulty or severe weakness, contact your veterinarian immediately.
- This drug can cause a sudden drop in heart rate, so it is usually given in the clinic where your pet can be closely monitored.
- Do not give any other medications without consulting your vet, as many drugs can interact with neostigmine.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.