Xylazine (BAY 1470) is a potent agonist of α2-adrenergic receptors and is widely used as a sedative in veterinary medicine. It can also induce muscle relaxation[1, 2]. Xylazine is often co-administered with ketamine for safe and effective anesthesia of small experimental animals[3].
In vitro, Xylazine (0.9, 1.8, 2.7, 3.6, 4.5, 5.4, 6.3μM) treatment of PC12 cells for 3h significantly reduced cell viability. When the dose was 4.5μM, the cell survival rate was 61%. It also inhibited the expression of extracellular regulated protein kinase (ERK) and protein kinase A (PKA)[4]. Xylazine (1, 4, 25mg/mL) was used to treat horse articular chondrocytes for 15min, which reduced cell viability in a dose-dependent manner. At a dose of 25mg/mL, cells showed apoptotic morphologies such as cell shrinkage, membrane blebbing, nuclear chromatin condensation, and nuclear fragmentation[5].
In vivo, Xylazine (5.2mg/kg) was used to treat SD rats by intraperitoneal injection for 10-60min. When the rats were killed 40min after administration, the mRNA level of liver kinase B1 (LKB1) in the brainstem was significantly reduced, while the mRNA level of LKB1 in the cerebral cortex, hippocampus, thalamus, and cerebellum was significantly increased[6].
References:
[1] Park J W, Chung H W, Lee E J, et al. α2-Adrenergic agonists including xylazine and dexmedetomidine inhibit norepinephrine transporter function in SK-N-SH cells[J]. Neuroscience Letters, 2013, 541: 184-189.
[2] Da Silveira J G, Cappelari B E, Varela A P M, et al. Evaluation of the effects of acepromazine and xylazine on viability in an equine dermal cell line[J]. Acta Veterinaria Brasilica, 2020, 14(4).
[3] Saha J K, Xia J, Grondin J M, et al. Acute hyperglycemia induced by ketamine/xylazine anesthesia in rats: mechanisms and implications for preclinical models[J]. Experimental Biology and Medicine, 2005, 230(10): 777-784.
[4] Zhao J, Zhang Y, Liu W, et al. Molecular mechanisms of the sedation and analgesia induced by xylazine on Wistar rats and PC12 cell[J]. Experimental animals, 2019, 68(3): 351-360.
[5] Mancini F, Nannarone S, Buratta S, et al. Effects of xylazine and dexmedetomidine on equine articular chondrocytes in vitro[J]. Veterinary anaesthesia and analgesia, 2017, 44(2): 295-308.
[6] Shi X X, Yin B S, Yang P, et al. Xylazine activates adenosine monophosphate-activated protein kinase pathway in the central nervous system of rats[J]. PLoS One, 2016, 11(4): e0153169.