Neostigmine

Neostigmine is a reversible acetylcholinesterase inhibitor with predominantly peripheral actions. It is used to improve neuromuscular transmission, reverse selected nondepolarizing muscle relaxants and stimulate smooth-muscle activity in some functional motility disorders. Its poor penetration into the brain distinguishes it from physostigmine and helps define its clinical role.

Group

Peripheral acetylcholinesterase inhibitor

Mechanism of Action

Neostigmine carbamylates acetylcholinesterase and temporarily reduces acetylcholine breakdown. Increased acetylcholine at neuromuscular junctions improves activation of skeletal-muscle nicotinic receptors and can overcome competitive neuromuscular blockade. Increased acetylcholine at muscarinic sites stimulates gastrointestinal and bladder smooth muscle and secretions. These effects remain principally peripheral because the charged molecule crosses the blood–brain barrier poorly.

Dose Rates

Dogs

Use / stage	Dose	Route	Schedule	Instructions
Oral antimyasthenic treatment	Reference only	PO		Total 2 mg/kg/day orally in divided doses; the number and spacing of doses are not specified.
Antimyasthenic treatment	10 mcg/kg	IM, SC	As needed	Not intended for prolonged maintenance.
Neuromuscular blockade reversal	40 mcg/kg	IM, SC	As needed
Myasthenia diagnostic aid	40 mcg/kg	IM	Once
Myasthenia diagnostic aid	20 mcg/kg	IV	Once
Antimyasthenic treatment	0.04 mg/kg	IM	Every 6 h	Alternative when regurgitation prevents oral dosing.
Myasthenia diagnostic aid	0.05 mg/kg	IM	Once	Pretreat with atropine; improvement is expected within 15-30 minutes if responsive.
Neuromuscular blockade reversal	0.001 mg/kg	SC		Curare overdose report; followed by atropine 0.04 mg/kg IV.

Cats

Use / stage	Dose	Route	Schedule	Instructions
Oral antimyasthenic treatment	Reference only	PO		Total 2 mg/kg/day orally in divided doses; the number and spacing of doses are not specified.
Antimyasthenic treatment	10 mcg/kg	IM, SC	As needed	Not intended for prolonged maintenance.
Neuromuscular blockade reversal	40 mcg/kg	IM, SC	As needed
Myasthenia diagnostic aid	40 mcg/kg	IM	Once
Myasthenia diagnostic aid	20 mcg/kg	IV	Once
Antimyasthenic treatment	0.04 mg/kg	IM	Every 6 h	Alternative when regurgitation prevents oral dosing.

Horses

Use / stage	Dose	Route	Schedule	Instructions
Motility stimulation	0.02–0.04 mg/kg	IV, SC		Repeat according to response.
Motility stimulation	0.008 mg/kg/hour	IV	Continuous
Motility stimulation	0.0220462262 mg/kg	SC	As needed	1 mg per 100 lb; exact pound-to-kilogram conversion.
Colonic ileus	0.022 mg/kg	IV
Colonic ileus	0.044 mg/kg	SC, IM
Colonic ileus	0.025 mg/kg	SC	Every 2–6 h
Foal colonic distension	1–2 mg/animal	SC	Every 1 h	Foals with C. perfringens type C-associated distension; 2-3 initial doses then as needed. Foals over 250 lb receive 2 mg.

Cattle

Use / stage	Dose	Route	Schedule	Instructions
Motility stimulation	0.022 mg/kg	SC
Motility stimulation	0.0220462262 mg/kg	SC	As needed	1 mg per 100 lb; exact pound-to-kilogram conversion.

Sheep

Use / stage	Dose	Route	Schedule	Instructions
Motility stimulation	0.022–0.033 mg/kg	SC

Pigs

Use / stage	Dose	Route	Schedule	Instructions
Motility stimulation	0.044–0.066 mg/kg	IM

Ruminant

Use / stage	Dose	Route	Schedule	Instructions
Rumen hypomotility	0.02 mg/kg	IM, SC

Indications

Treatment of selected myasthenia gravis patients requiring short-acting peripheral anticholinesterase support.
Reversal of selected nondepolarizing neuromuscular blockade in anesthetized veterinary patients.
Empirical treatment of selected functional gastrointestinal hypomotility, including some colonic ileus or ruminal atony cases.
Treatment of selected functional urinary retention associated with inadequate bladder contraction.
Specialist diagnostic assessment of suspected myasthenia gravis using a pharmacologic response test.

Contraindications

Mechanical urinary or intestinal obstruction
Asthma or bronchoconstriction, pneumonia, or cardiac arrhythmias
Bromide sensitivity applies to bromide formulations; additional bromide can accumulate with potassium bromide.

Interactions

Other cholinergic drugs increase toxicity; atropine and glycopyrrolate oppose muscarinic effects.

Adverse effects

Diarrhea, secretions, bradycardia, miosis, bronchoconstriction and muscle weakness.

Toxicity

Excess cholinergic effects may require atropine and supportive treatment. Cholinergic crisis causes secretions, bronchospasm, bradycardia or tachycardia, weakness and possible respiratory paralysis. Stop treatment, distinguish from myasthenic deterioration, support ventilation and use atropine for muscarinic effects.

Preparations

Preparation	Form	Strength	Route
Neostigmine bromide 15 mg	Tablet	15 mg / tablet	PO
Neostigmine methylsulfate 0.25 mg/mL	Injection	0.25 mg / mL	IV, IM, SC
Neostigmine methylsulfate 0.5 mg/mL	Injection	0.5 mg / mL	IV, IM, SC
Neostigmine methylsulfate 1 mg/mL	Injection	1 mg / mL	IV, IM, SC

Monitoring and Administration

Monitor gastrointestinal signs, pulse and rhythm. Equine use may worsen abdominal discomfort; pyridostigmine is often preferred for ongoing myasthenia treatment.

A conflicting small-intestinal ileus report describes 2 mg per 500-kg adult horse SC or IV every 30-60 minutes to cumulative 10 mg; other guidance says no small-intestinal benefit. Keep cumulative and weight-qualified context; colic may worsen.

Protect neostigmine methylsulfate injection from light and freezing; bromide tablets remain a different salt.