Atipamezole
Atipamezole is a highly specific and potent **alpha-2 adrenergic antagonist** primarily used in veterinary medicine as a reversal agent for alpha-2 agonists such as medetomidine and dexmedetomidine. It may also be used off-label to reverse other alpha-2 agonists like xylazine, amitraz, and clonidine. **Clinical Pearls:** * Atipamezole has an $\alpha_2:\alpha_1$ selectivity ratio of 8526:1, making it significantly more specific than older reversal agents like yohimbine or tolazoline. This high specificity results in a rapid, clean reversal with fewer cardiovascular side effects. * Because it rapidly reverses both sedation **and analgesia**, patients must be evaluated for pain prior to administration, and alternative analgesics (e.g., opioids, NSAIDs) should be provided if the patient has undergone a painful procedure. * The half-life of atipamezole is relatively short (2-3 hours in dogs). When treating toxicities from long-acting alpha-2 agonists (like amitraz), the offending agent may outlast the reversal agent, leading to re-sedation and requiring repeated dosing.
Mechanism: Atipamezole competitively binds to central and peripheral **$\alpha_2$-adrenergic receptors**, displacing alpha-2 agonists. By blocking these receptors, it inhibits the negative feedback loop on presynaptic neurons $\rightarrow$ increases the release of **norepinephrine** into the synaptic cleft $\rightarrow$ leads to rapid arousal, reversal of sedation, increased heart rate, increased blood pressure, and loss of analgesia. It also antagonizes the diuretic action of alpha-2 agonists like xylazine.
Dosing by species
- For reversal of alpha2-adrenergic agonists in caprine species · 0.02-0.1 mg/kg IV to effect · IV · Once
- Small ruminants · 0.1-0.2 mg/kg slow IV or IM · IV/IM · Once · As a rule of thumb, if induction included ketamine or Telazol do not reverse alpha2 sooner than 30 and ideally 60 minutes after induction. This will allow enough of the ketamine or tiletamine to be metabolized.
- For reversal of alpha2-adrenergic agonists in ovine species · 0.02-0.1 mg/kg IV to effect · IV · Once
- Small ruminants · 0.1-0.2 mg/kg slow IV or IM · IV/IM · Once · As a rule of thumb, if induction included ketamine or Telazol do not reverse alpha2 sooner than 30 and ideally 60 minutes after induction. This will allow enough of the ketamine or tiletamine to be metabolized.
- For reversal of medetomidine · Give IM an equal volume of Antisedan® and Domitor® is administered (mL per mL). The actual concentration of Antisedan® will be 5X that of Domitor®, as Antisedan® is 5 mg/mL versus Domitor®'s 1 mg/mL. · IM · Once
- For reversal of medetomidine · As above, but may give IV as well as IM. If it has been at least 45 minutes since medetomidine was given, may give atipamezole at half the volume of medetomidine if administered IV. If after 10-15 minutes an IM dose of atipamezole has not seemed to reverse the effects of medetomidine, an additional dose of atipamezole at 1/2 the volume of the medetomidine dose may be given. · IV/IM · Once, may repeat
- For reversal of dexmedetomidine · 0.2 mg/kg IM or IV · IM/IV · Once
Routes of administration
Contraindications
- Reptiles (Intravenous administration is contraindicated due to profound hypotension)
Adverse effects
- Vomiting
- Diarrhea
- Hypersalivation
- Tremors
- Brief excitation or apprehensiveness
- Aggression upon rapid waking
- Profound hypotension (if given IV in reptiles)
- Loss of analgesia
Drug interactions
- Alpha-1 adrenergic blockers (e.g., prazosin) · Atipamezole can partially block alpha-1 receptors and reduce the effects of prazosin.
- Alpha-2 adrenergic agonists (e.g., detomidine, clonidine, brimonidine, xylazine, amitraz) · Atipamezole can reduce the effects (toxic or therapeutic) of these agents.
- Medetomidine · Reverses sedative, analgesic, and cardiovascular effects (intended therapeutic interaction) · minor
- Dexmedetomidine · Reverses sedative, analgesic, and cardiovascular effects (intended therapeutic interaction) · minor
- Ketamine · If atipamezole is given less than 30 minutes after a medetomidine/ketamine combination in cats, it can cause severe CNS excitation during recovery. · major
- Other alpha-2 antagonists · Additive antagonistic effects · moderate
- Hypotensive agents · May exacerbate transient hypotension · minor
Monitoring
- Level of sedation and analgesia
- Heart rate
- Body temperature
Overdose
Dogs receiving up to 10X the listed dosage apparently tolerated the drug without major effects. **Clinical signs of overdose:** * Panting * Excitement * Trembling * Vomiting * Soft or liquid feces * Vasodilatation of sclera * Muscle injury at the IM injection site Specific overdose therapy should generally not be necessary as effects are typically transient.
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.