The α2A‐adrenoceptor subtype plays a key role in the analgesic and sedative effects of xylazine

AbstractXylazine, the classical α2‐adrenoceptor (α2‐AR) agonist, is still used as an analgesic and sedative in veterinary medicine, despite its low potency and affinity for α2‐ARs. Previous pharmacological studies suggested that the α2A‐AR subtype plays a role in mediating the clinical effects of xylazine; however, these studies were hampered by the poor subtype‐selectivity of the antagonists used and a lack of knowledge of their bioavailability in vivo. Here, we attempted to elucidate the role of the α2A‐AR subtype in mediating the clinical effects of xylazine by comparing the analgesic and sedative effects of this drug in wild‐type mice with those in α2A‐AR functional knockout mice using the hot‐plate and open field tests, respectively. Hippocampal noradrenaline turnover in both mice was also measured to evaluate the contribution of α2A‐AR subtype to the inhibitory effect of xylazine on presynaptic noradrenaline release. In wild‐type mice, xylazine (10 or 30 mg/kg) increased the hot‐plate latency. Furthermore, xylazine (3 or 10 mg/kg) inhibited the open field locomotor activity and decreased hippocampal noradrenaline turno ver. By contrast, all of these effects were abolished in α2A‐AR functional knockout mice. These results indicate that the α2A‐AR subtype is mainly responsible for the clinical effects of xylazine.
Source: Journal of Veterinary Pharmacology and Therapeutics - Category: Veterinary Research Authors: Tags: SHORT COMMUNICATION Source Type: research