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.
Xylazine（赛拉嗪；BAY 1470）是一种有效的α2-肾上腺素受体的强激动剂，在兽医学中广泛用作镇静剂，还能诱导肌肉松弛[1, 2]。Xylazine常与氯胺酮（Ketamine）联合给药，用于安全、有效地麻醉小型实验动物[3]。
在体外，Xylazine（0.9, 1.8, 2.7, 3.6, 4.5, 5.4, 6.3μM）处理PC12细胞3h，显著降低了细胞活力，使用剂量为4.5μM时，细胞存活率为61%，还抑制了细胞外调节蛋白激酶（ERK）和蛋白激酶A（PKA）的表达[4]。Xylazine（1，4，25mg/mL）处理马关节软骨细胞15min，以剂量依赖性方式降低了细胞活力，使用剂量为25mg/mL时，细胞表现出细胞收缩、膜起泡、核染色质浓缩和核碎裂等凋亡形态[5]。
在体内，Xylazine（5.2mg/kg）通过腹腔注射处理SD大鼠10-60min，当给药40min后再处死大鼠，显著降低了脑干中肝激酶B1（LKB1）的mRNA水平，而大脑皮层、海马、丘脑和小脑中LKB1的mRNA水平显著升高[6]。