Lidocaine hydrochloride (Lignocaine hydrochloride) is an amino-amide-type local anaesthetic that inhibits voltage-insensitive ‘flicker’ K+ channel with an IC50 value of 220μM[1]. Lidocaine hydrochloride can cross the blood-brain barrier through passive diffusion across membranes and cause the blockade of voltage-gated sodium channels (VGSCs), leading to a reversible block of action potential propagation [2]. Lidocaine hydrochloride has been widely used in disease models for pain suppression and anti-inflammatory and anti-injury[3].
In vitro, Lidocaine hydrochloride treatment for 24h inhibited the viability of CCD-1064sk cells with an IC50 value of 613.77µM[4]. Treatment of SH-SY5Y cells with 10mM Lidocaine hydrochloride for 24h resulted in morphological changes, induced apoptosis, and significantly increased the amount of LDH released into the culture medium[5]. Treatment with 5μM Lidocaine hydrochloride for 24h attenuated cytokine-induced endothelial and vascular smooth muscle cell injury and increased cell survival[6].
In vivo, Lidocaine hydrochloride treatment (30mg/kg; twice a week) via intraperitoneal injection for 30 days reduced the tumor growth of HepG2 cell xenografts in nude mice without affecting body weight[7]. Subcutaneous injection of Lidocaine hydrochloride (30mg/kg) at 12-hour intervals for 3 days rescued the contractile function of the ischemic myocardial region in a mouse model of persistent myocardial ischemia without affecting cardiomyocyte death[8].
References:
[1] Hermanns H, Hollmann M W, Stevens M F, et al. Molecular mechanisms of action of systemic lidocaine in acute and chronic pain: a narrative review[J]. British journal of anaesthesia, 2019, 123(3): 335-349.
[2] Moreira-Junior L, Leal-Cardoso J H, Cassola A C, et al. Eugenol and lidocaine inhibit voltage-gated Na+ channels from dorsal root ganglion neurons with different mechanisms[J]. Frontiers in Pharmacology, 2024, 15: 1354737.
[3] Karnina R, Arif S K, Hatta M, et al. Molecular mechanisms of lidocaine[J]. Annals of Medicine and Surgery, 2021, 69: 102733.
[4] Choi W, Ryu H, Fuwad A, et al. Quantitative analysis of the membrane affinity of local anesthetics using a model cell membrane[J]. Membranes, 2021, 11(8): 579.
[5] Friederich P, Schmitz T P. Lidocaine-induced cell death in a human model of neuronal apoptosis[J]. European journal of anaesthesiology, 2002, 19(8): 564-570.
[6] de Klaver M J M, Buckingham M G, Rich G F. Lidocaine attenuates cytokine-induced cell injury in endothelial and vascular smooth muscle cells[J]. Anesthesia & Analgesia, 2003, 97(2): 465-470.
[7] Xing W, Chen D T, Pan J H, et al. Lidocaine induces apoptosis and suppresses tumor growth in human hepatocellular carcinoma cells in vitro and in a xenograft model in vivo[J]. Anesthesiology, 2017, 126(5): 868-881.
[8] Müller-Edenborn B, Kania G, Osto E, et al. Lidocaine enhances contractile function of ischemic myocardial regions in mouse model of sustained myocardial ischemia[J]. PloS one, 2016, 11(5): e0154699.
Lidocaine hydrochloride (Lignocaine hydrochloride)是一种氨基酰胺类局部麻醉剂，可抑制voltage-insensitive ‘flicker’ K+ channel，IC50值为220μM[1]。Lidocaine hydrochloride通过被动扩散跨膜透过血脑屏障，阻断电压门控钠通道（VGSCs），导致动作电位传播的可逆性阻滞[2]。Lidocaine hydrochloride已广泛应用于疾病模型的镇痛、抗炎和抗损伤研究[3]。
在体外，Lidocaine hydrochloride处理24小时可抑制CCD-1064sk细胞活力，IC50值为613.77µM[4]。10mM的Lidocaine hydrochloride处理SH-SY5Y细胞24小时会引起形态学改变、诱导细胞凋亡，并显著增加培养基中LDH释放量[5]。5μM的Lidocaine hydrochloride处理24小时能减轻细胞因子诱导的内皮细胞和血管平滑肌细胞损伤，提高细胞存活率[6]。
在体内，裸鼠腹腔注射Lidocaine hydrochloride（30mg/kg；每周两次；持续30天）可抑制HepG2细胞异种移植瘤的生长且不影响体重[7]。持续性心肌缺血小鼠模型每隔12小时皮下注射30mg/kg剂量的Lidocaine hydrochloride（持续3天）能恢复缺血心肌区域的收缩功能，且不影响心肌细胞死亡[8]。