Physostigmine

Physostigmine is a reversible acetylcholinesterase inhibitor that enters the central nervous system. This distinguishes it from predominantly peripheral anticholinesterases such as neostigmine. Its principal toxicologic application is reversal of selected antimuscarinic syndromes, while other motility or neuromuscular applications in veterinary medicine have a more limited and largely historical evidence base.

Group

Central and peripheral acetylcholinesterase inhibitor

Mechanism of Action

Physostigmine temporarily inhibits acetylcholinesterase, increasing the amount and duration of acetylcholine at cholinergic synapses. Because it crosses the blood–brain barrier, it can restore cholinergic signaling in both central and peripheral antimuscarinic intoxication. Increased acetylcholine also enhances nicotinic neuromuscular transmission and muscarinic smooth-muscle activity, accounting for additional peripheral effects.

Dose Rates

Dogs

Use / stage	Dose	Route	Schedule	Instructions
Anticholinergic intoxication	0.02 mg/kg	IV	Every 12 h
Ivermectin CNS depression diagnostic adjunct	1 mg/animal	IV	Every 12 h	Transient response may last 30-90 minutes; not definitive antidotal therapy and may provoke seizure-like activity in less-depressed dogs.
Narcolepsy diagnostic challenge	0.025 mg/kg	IV		Observe response to a food/stimulus test after 9-15 minutes; higher sequential challenges are separate protocols.
Narcolepsy diagnostic challenge	0.05 mg/kg	IV		Observe response to a food/stimulus test after 9-15 minutes; higher sequential challenges are separate protocols.

Cats

Use / stage	Dose	Route	Schedule	Instructions
Anticholinergic intoxication	0.02 mg/kg	IV	Every 12 h

Horses

Use / stage	Dose	Route	Schedule	Instructions
Narcolepsy diagnostic challenge	0.05–0.1 mg/kg	IV		Slow administration; colic/cholinergic signs possible and a negative challenge does not exclude narcolepsy.
Narcolepsy diagnostic challenge	0.06–0.08 mg/kg	IV		Slow administration; colic/cholinergic signs possible and a negative challenge does not exclude narcolepsy.

Cattle

Use / stage	Dose	Route	Schedule	Instructions
Larkspur poisoning adjunct	0.04–0.08 mg/kg	IV	As needed	Historical serial-injection report; monitor cardiac and cholinergic effects.

Indications

Specialist treatment of selected central and peripheral antimuscarinic intoxications, including suitable atropine-like drug exposures.
Historical reversal of selected nondepolarizing neuromuscular blockade, with more limited veterinary use than peripheral reversal agents.
Historical treatment of selected functional ileus or urinary retention, with limited controlled clinical evidence.

Contraindications

Avoid concurrent choline esters such as bethanechol.

Interactions

Other cholinergic drugs amplify toxicity.

Adverse effects

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

Toxicity

Atropine can counter excessive muscarinic effects. Severe cholinergic toxicity can compromise breathing; discontinue exposure, support ventilation/airway clearance and treat muscarinic effects with atropine. Additional antidotal measures require a specific toxicologic plan.

Preparations

Preparation	Form	Strength	Route
Physostigmine injection 1 mg/mL	Injection	1 mg / mL	IV

Monitoring and Administration

Monitor rhythm, heart rate and gastrointestinal effects. For prolonged anticholinesterase treatment, alternatives with fewer central effects may be preferable.