Atipamezole Hydrochloride

 

General Information

Atipamezole hydrochloride is an alpha-two antagonist for use in reversing the effects of
alpha-two agonists such as xylazine hydrochloride, medetomidine hydrochloride and
dexmedetomidine sedation. Atipamezole hydrochloride was approved under the trade
name Antisedan in 1996 from Pfizer Animal Health.

 

Use in Wildlife Management

Atipamezole hydrochloride is uniquely effective for reversal of alpha-two sedation in nondomestic hoofstock and most other wild and exotic species. The ability of yohimbine hydrochloride or tolazoline hydrochloride to effectively reverse alpha-two sedation by xylazine hydrochloride or the more specific binding medetomidine hydrochloride and dexmedetomidine varies among species. Species such as blackbuck and argali sedated with xylazine hydrochloride are difficult to reverse with yohimbine hydrochloride or tolazoline hydrochloride but reverse rapidly with atipamezole hydrochloride. Similar difficulties occur with hoofstock that are hand reared and/or imprinted and do not respond favorably to reversal of alpha-twos with yohimbine hydrochloride or tolazoline hydrochloride. These animals usually can be reversed with atipamezole hydrochloride.

 

In zoo and wildlife work it is not uncommon to see resedation of hoof stock 3-4 hours after an immobilization that utilizes an alpha-two agonist in the protocol. By having 20 mg/ml atipamezole available enough can be remotely administered by dart to effectively deal with any resedation problem. Additionally the 20 mg/ml concentration allows for a lower dose volume to be administered to the animal.

 

Chemistry, Metabolism, and Pharmacology

Atipamezole is 4-(2-Ethyl-1,3-dihydroinden-2-yl)-3H-imidazole with a chemical formula of C₁₄H₁₆N₂.

 

Atipamezole hydrochloride is a weak lipophilic base (1.) Absorption after intramuscular
administration is rapid; a peak plasma level is reached in about 10 minutes in dogs (2.) Peak concentrations in tissue, including the brain, are two to three times higher than corresponding plasma levels (3.) Atipamezole hydrochloride rapidly crosses the blood– brain barrier. The drug undergoes extensive hepatic biotransformation, and metabolites are primarily excreted in urine (3.) The elimination half-life is 1.3 hours in rats and 2.6 hours in dogs (3), (4.)

 

Atipamezole hydrochloride has a high affinity for all three α2-adrenergic receptor subtypes in both humans and rodents (3.) It competitively displaces α2-adrenergic agonist drugs and rapidly blocks or reverses several drug effects. Atipamezole hydrochloride is more potent and selective than other α2-antagonists (e.g., yohimbine hydrochloride, tolazoline hydrochloride). Receptor binding studies in rodents have shown the α2-to-α1 selectivity ratio of atipamezole to be 8526 compared with 3240, 1620, 260, and 160 for dexmedetomidine, medetomidine hydrochloride, detomidine, and xylazine hydrochloride, respectively (3) (5.) The α2-to-α1 selectivity ratio for yohimbine hydrochloride, an indole alkaloid, is 40 (3.) Atipamezole hydrochloride is highly selective: studies based on receptor binding and conducted using isolated organ preparations have shown that atipamezole hydrochloride has no affinity for or effects on other receptors (e.g., histaminergic, opiate, muscarinic, serotoninergic, dopaminergic, GABAergic, or benzodiazepine receptors). This selectivity minimizes the undesirable effects (5.)

1. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th ed.
   Whitehouse Station,NJ:Merck & Co; 2001:148.
2. Plumb DC. Atipamezole. Veterinary Drug Handbook. 4th ed. Ames, IA: Iowa State University Press; 2002:76-77.
3. Bialer M, Johannessen SI, Kupferberg HJ, et al. Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII). Epilepsy Res 2004;61:1-48.
4. Virtanen R. Pharmacology of detomidine and other α2-adrenoreceptor agonists in the brain. Acta Vet Scand 1986;(82):35-46.
5. Virtanen R, Savola JM, Saano V. Highly selective and specific antagonism of central and peripheral alpha 2-adrenoceptors
   by atipamezole. Arch Int Pharmacodyn Ther 1989;297:190-204.

Dose Recommendations

Atipamezole hydrochloride is dosed as a ratio to the amount of medetomidine
hydrochloride administered. The dose ratio to medetomidine hydrochloride ranges
from 3/1 to 10/1 in the wide range of species. In most species it is 5/1. Atipamezole
hydrochloride is always given intramuscularly. Intravenous use is for absolute anesthetic emergencies only.

 

Formulations Available

Atipamezole hydrochloride is compounded upon prescription in 10 ml multiple use vials. Each ml contains 20 mg of atipamezole hydrochloride.