Atipamezole

Atipamezole is a selective alpha2-adrenergic antagonist used to reverse the effects of alpha2-agonist sedatives. Its main veterinary application is reversal of medetomidine or dexmedetomidine in dogs, with additional species-specific and extra-label uses. It also has a role in selected intoxications that produce clinically important alpha2-mediated effects.

Group

Alpha-2 adrenergic antagonist

Mechanism of Action

Atipamezole competitively blocks alpha2-adrenoceptors and removes agonist-induced inhibition of norepinephrine release. Restoration of noradrenergic signaling promotes arousal and reverses alpha2-mediated sedation, analgesia and autonomic changes. The degree of reversal depends on receptor occupancy, the agonist involved and concurrent drugs. In amitraz intoxication, antagonism addresses the alpha2 activity of amitraz and its metabolites.

Dose Rates

Dogs

Use / stage	Dose	Route	Schedule	Instructions
Dexmedetomidine reversal	0.2 mg/kg	IM, IV	Once
Amitraz toxicosis	0.05 mg/kg	IM	Every 4–6 h	Reassess for recurrence because amitraz may outlast the antagonist.
Medetomidine reversal	Reference only	IM		For 5 mg/mL atipamezole and 1 mg/mL medetomidine, the source describes equal IM volumes. Prior agonist dose determines antagonist amount; retain the concentration-specific ratio.

Cats

Use / stage	Dose	Route	Schedule	Instructions
Dexmedetomidine reversal	0.2 mg/kg	IM, IV	Once
Medetomidine reversal	Reference only	IM		For 5 mg/mL atipamezole and 1 mg/mL medetomidine, the source describes equal IM volumes. Prior agonist dose determines antagonist amount; retain the concentration-specific ratio.

Rabbits

Use / stage	Dose	Route	Schedule	Instructions
Medetomidine reversal	0.5 mg/kg	IM, SC	Once
Medetomidine reversal	0.25 mg/kg	IV	Once

Mice

Use / stage	Dose	Route	Schedule	Instructions
Alpha-2 agonist reversal	0.1–1 mg/kg	IM, IP, IV, SC	Once

Rats

Use / stage	Dose	Route	Schedule	Instructions
Alpha-2 agonist reversal	0.1–1 mg/kg	IM, IP, IV, SC	Once

Gerbils

Use / stage	Dose	Route	Schedule	Instructions
Alpha-2 agonist reversal	0.1–1 mg/kg	IM, IP, IV, SC	Once

Hamsters

Use / stage	Dose	Route	Schedule	Instructions
Alpha-2 agonist reversal	0.1–1 mg/kg	IM, IP, IV, SC	Once

Guinea pigs

Use / stage	Dose	Route	Schedule	Instructions
Alpha-2 agonist reversal	0.1–1 mg/kg	IM, IP, IV, SC	Once

Cattle

Use / stage	Dose	Route	Schedule	Instructions
Alpha-2 agonist reversal	0.02–0.1 mg/kg	IV	Once	Titrate to effect.

Sheep

Use / stage	Dose	Route	Schedule	Instructions
Alpha-2 agonist reversal	0.02–0.1 mg/kg	IV	Once	Titrate to effect.
Alpha-2 agonist reversal - alternative	0.1–0.2 mg/kg	IV, IM	Once	If IV, give slowly; observe the delay after dissociative combinations.

Goats

Use / stage	Dose	Route	Schedule	Instructions
Alpha-2 agonist reversal	0.02–0.1 mg/kg	IV	Once	Titrate to effect.
Alpha-2 agonist reversal - alternative	0.1–0.2 mg/kg	IV, IM	Once	If IV, give slowly; observe the delay after dissociative combinations.

Llamas

Use / stage	Dose	Route	Schedule	Instructions
Alpha-2 agonist reversal	0.02–0.1 mg/kg	IV	Once	Titrate to effect.
Alpha-2 agonist reversal - alternative	0.1–0.2 mg/kg	IV, IM	Once	If IV, give slowly; observe the delay after dissociative combinations.

Alpacas

Use / stage	Dose	Route	Schedule	Instructions
Alpha-2 agonist reversal	0.02–0.1 mg/kg	IV	Once	Titrate to effect.
Alpha-2 agonist reversal - alternative	0.1–0.2 mg/kg	IV, IM	Once	If IV, give slowly; observe the delay after dissociative combinations.

Birds

Use / stage	Dose	Route	Schedule	Instructions
Alpha-2 agonist reversal	0.5 mg/kg	IM	Once

Reptiles

Use / stage	Dose	Route	Schedule	Instructions
Medetomidine reversal	Reference only	IM		Atipamezole amount 4-5 times the medetomidine dose in the ketamine/medetomidine protocol; reversal may take up to one hour. Do not give IV.

Indications

Reversal of medetomidine- or dexmedetomidine-associated sedation and related effects in dogs.
Reversal of selected alpha2-agonist effects in cats, horses or other veterinary species using a supported protocol.
Adjunctive reversal of clinically significant alpha2-mediated effects in selected amitraz poisoning.
Specialist treatment of selected intoxications involving other alpha2 agonists, with agent-specific evidence.

Contraindications

Avoid IV administration in reptiles because profound hypotension can occur.
Pregnancy, lactation and breeding safety are inadequately established.

Interactions

Antagonises alpha-2 agonists; removal of their analgesia may expose untreated pain.
Partial alpha-1 effects may interfere with prazosin.

Adverse effects

Vomiting, diarrhoea, salivation, tremor and abrupt excitation or aggression.

Toxicity

Overdose usually causes transient excitement, panting, vomiting or tremor. Monitor cardiovascular status.

Preparations

Preparation	Form	Strength	Route
Antisedan 5 mg/mL Strength expressed as atipamezole hydrochloride. Source IV protocols are extralabel and do not change the labelled product route.	Injection	5 mg / mL	IM

Monitoring and Administration

Provide alternative analgesia before reversing a painful patient. Protect recovering animals from falls and observe for resedation.

After ketamine/tiletamine combinations in small ruminants or camelids, do not reverse too early: allow at least 30, preferably 60, minutes for the dissociative component to diminish.

The equal-volume rule applies only to the specified agonist and antagonist concentrations; it is not a universal volume rule.