Antagonistic effect of flumazenil on tiletamine-zolazepam-induced anaesthesia in Beagle dogs

Benzodiazepines exert hypnotic/sedative effects through their inhibitory actions on the γ-aminobutyric acid receptor type A. Since flumazenil antagonises these effects through competitive inhibition of the receptor, it has been used to reverse the effect of benzodiazepines. The goal of this study was to characterise the antagonistic effect of flumazenil on anaesthesia induced by tiletamine-zolazepam in dogs. Nine healthy Beagle dogs (four males, five females) were used in this study. The dogs were administered 20 mg/kg of tiletamine-zolazepam intravenously and were then intravenously treated with saline solution (2 ml; control) or flumazenil twenty minutes after tiletamine-zolazepam administration at doses of 0.02, 0.04, 0.06, 0.08 or 0.16 mg/kg. Recovery times after the anaesthesia and cardiorespiratory variation were recorded for each dog. The results of this study indicate that the duration of reversal produced by doses of 0.04 and 0.06 mg/kg flumazenil was more effective than that produced by any of the other doses. In addition, sedation was rapidly reversible at 0.04 and 0.06 mg/kg without resedation. However, at doses of 0.08 and 0.16 mg/kg adverse effects such as shivering, rigidity and opisthotonos were observed. Thus, treatment with flumazenil at doses of 0.04 and 0.06 mg/kg could successfully reverse the anaesthetic effects induced by tiletamine-zolazepam.