open access

https://hdl.handle.net/2115/76848

The alpha(2A)-adrenoceptor subtype plays a key role in the analgesic and sedative effects of xylazine

英語

xylazine

2019-03

John Wiley & Sons

Journal of veterinary pharmacology and therapeutics

42(2)

243-247

Xylazine, the classical alpha(2)-adrenoceptor (alpha(2)-AR) agonist, is still used as an analgesic and sedative in veterinary medicine, despite its low potency and affinity for alpha(2)-ARs. Previous pharmacological studies suggested that the alpha(2A)-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 alpha(2A)-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 alpha(2A)-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 alpha(2A)-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 turnover. By contrast, all of these effects were abolished in alpha(2A)-AR functional knockout mice. These results indicate that the alpha(2A)-AR subtype is mainly responsible for the clinical effects of xylazine.

学術雑誌論文

Accepted Manuscript

This is the peer reviewed version of the following This This is the peer reviewed version of the following article: https://onlinelibrary.wiley.com/doi/full/10.1111/jvp.12724, which has been published in final form at　https://onlinelibrary.wiley.com/doi/full/10.1111/jvp.12724 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

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