|
Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine >
Peer-reviewed Journal Articles, etc >
The alpha(2A)-adrenoceptor subtype plays a key role in the analgesic and sedative effects of xylazine
| Title: | The alpha(2A)-adrenoceptor subtype plays a key role in the analgesic and sedative effects of xylazine |
| Authors: | Kitano, Taisuke Browse this author | | Kobayashi, Takeshi Browse this author | | Yamaguchi, Soichiro Browse this author | | Otsuguro, Ken-ichi Browse this author →KAKEN DB |
| Keywords: | alpha(2A)-Adrenoceptor | | analgesics | | sedatives | | xylazine |
| Issue Date: | Mar-2019 |
| Publisher: | John Wiley & Sons |
| Journal Title: | Journal of veterinary pharmacology and therapeutics |
| Volume: | 42 |
| Issue: | 2 |
| Start Page: | 243 |
| End Page: | 247 |
| Publisher DOI: | 10.1111/jvp.12724 |
| Abstract: | 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. |
| Rights: | 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. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/76848 |
| Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
Submitter: 乙黒 兼一
|
