A synthetic α2-adrenergic antagonist-Atipamezole hydrochloride

Description

Atipamezole is a potent and selective α2-receptor blocking agent (α2-antagonist), which promotes the release of the neurotransmitter noradrenaline in the central and peripheral nervous systems. This leads to activation of the central nervous system due to sympathetic activation.

ANTISEDAN (atipamezole hydrochloride) is a synthetic α2-adrenergic antagonist. The chemical name is 4-(2-ethyl-2,3-dihydro-1H-inden-2-yl)-1H-imidazole hydrochloride. As an α2-antagonist, atipamezole can eliminate (or inhibit) the effects of the α2-receptor agonist, medetomidine, or dexmedetomidine. Thus, atipamezole reverses the sedative effects of (dex)medetomidine hydrochloride in dogs and cats to normal and may lead to a transient increase in heart rate. Other pharmacodynamic effects, such as cardiovascular system influence, are only mild. However, a transient decrease in blood pressure may be seen within the first 10 minutes after injection of atipamezole hydrochloride.

pharmacokinetics

Atipamezole hydrochloride is rapidly absorbed after intramuscular injection. The maximal concentration in the central nervous system is reached in 10-15 minutes. The volume of distribution (Vd) is about 1 – 2.5 l/kg. The half-life of atipamezole hydrochloride is reported to be approximately 1 hour. Atipamezole hydrochloride is rapidly and completely metabolized. The metabolites are mainly excreted in urine and a small amount in feces.

Precautions 

1. Handling:

ANTISEDAN can produce an abrupt reversal of sedation; therefore, dogs that have recently received ANTISEDAN should be handled with caution. The potential for apprehensive or aggressive behavior should be considered in handling dogs emerging from sedation, especially in dogs predisposed to nervousness or fright. Also, avoid situations where a dog might fall.

2. Sedation relapse:

While atipamezole does reverse the clinical signs associated with medetomidine or dexmedetomidine sedation, a complete physiologic return to pretreatment status may not be immediate or may be temporary, and dogs should be monitored for sedation relapse. Sedation relapse is more likely to occur in dogs that receive an alpha2-agonist by the IV route compared to dogs that are sedated using the IM route. Animals should be monitored closely for persistent hypothermia, bradycardia, and depressed respiration until signs of recovery persist.

3. Analgesia reversal:

Atipamezole reverses analgesic effects as well as sedative effects. Additional procedures for the control of pain may be required.

4. Debilitated dogs:

The safety of atipamezole has not been evaluated in dogs with compromised health. Geriatric, debilitated, and ill dogs are more likely to experience adverse reactions associated with the administration of alpha2-antagonists (as well as alpha2-agonists). Dogs with abnormalities associated with the cardiovascular system are especially at risk.

5. Breeding dogs:

ANTISEDAN has not been evaluated in breeding dogs; therefore, the drug is not recommended for use in pregnant or lactating dogs or dogs intended for breeding.

6. Minimum age and weight:

ANTISEDAN has not been evaluated in dogs under four months of age or those weighing less than 4.4 lbs (2 kg).

References

[1] T Kauppila, A Pertovaara, E Jyväsjärvi. “Effects of atipamezole, an alpha 2-adrenoceptor antagonist, on the anesthesia induced by barbiturates and medetomidine.” Anesthesia and analgesia 75 3 (1992): 416–20.

[2] Licence_VPA10816-009-001_25062019080945.pdf (hpra.ie).

[3] ANTISEDAN® (atipamezole hydrochloride) (nih.gov).