Comparison of Atipamezole with Yohimbine for Antagonism of Xylazine in Mice Anesthetized with Ketamine and Xylazine.
The α2 adrenergic agonist xylazine produces a sedative effect and is typically combined with ketamine and used for anesthesia or chemical restraint of laboratory mice. Xylazine's sedative effect-and its undesirable side effects of bradycardia, hypotension, and poor tissue perfusion-can be reversed by administration of α2 antagonists, such as atipamezole or yohimbine. Although atipamezole and yohimbine dosing guidelines are available for mice, no controlled comparison has been performed to guide the lab animal community in the selection of one over the other. This study is a single-dose crossover comparison of these 2 antagonist drugs, given intraperitoneally at clinically recommended doses, to determine which results in more rapid recovery of mice from xylazine-ketamine anesthesia. Time to return of righting reflex was used as the primary outcome measure. Mice were anesthetized with xylazine (10 mg/kg IP) and ketamine (80 mg/kg IP), followed 15 min later by injection of an α2 antagonist or saline (control). Time to return of righting reflex differed significantly among groups, with mice recovering in an average of 10.3 min after administration of atipamezole (1 mg/kg IP) as compared with 21.3 min after yohimbine (1.5 mg/kg IP) and 38.2 min after saline. When rapid recovery of mice after xylazine-ketamine anesthesia is desirable, administration of an antagonist to reverse the effects of the xylazine is indicated. When injection of the antagonist by the technically simple intraperitoneal route is desirable, our data indicate that (at the doses evaluated) atipamezole is more effective than yohimbine.
Division of Laboratory Animal Resources, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, Center for Laboratory Animal Medicine and Care, University of Texas Health Science Center at Houston, Houston, Texas;, Email: Christopher.F.Janssen@uth.tmc.edu.
Christopher F
CF
Janssen
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Pauline
P
Maiello
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
M Jerry
MJ
Wright
Division of Laboratory Animal Resources, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Kara B
KB
Kracinovsky
Division of Laboratory Animal Resources, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Joseph T
JT
Newsome
D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D018592:Cross-Over Studies; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D007756:Laboratory Animal Science; D008297:Male; D051379:Mice; D014991:Xylazine / Q000008:administration & dosage / Q000494:pharmacology*; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D000700:Analgesics; D007093:Imidazoles; C050701:atipamezole; D014991:Xylazine; D015016:Yohimbine; D007649:Ketamine