Ivermectin is a macrolide endectocide with activity against both endoparasites and ectoparasites [1]. Ivermectin disrupts neurotransmission in nerve and muscle cells, causing hyperpolarisation of the neuronal membrane, inducing paralysis of somatic muscles, particularly the pharyngeal pump, killing the parasites [2]. Ivermectin has been widely used to inhibit parasitic infections and kill viruses[3].
In vitro, Ivermectin treatment for 48 hours significantly inhibited the proliferation of C6 cells and U251 cells, with IC50 values of 16.32µM and 14.58µM, respectively[4]. 2.5µM of Ivermectin treatment for 72 hours reduced the proliferation of Pseudorabies virus (PRV) in BHK-21 cells and inhibited the entry of PRV DNA polymerase auxiliary subunit UL42 into the cell nucleus[5].
In vivo, Ivermectin treatment via oral administration at a dose of 0.2mg/kg twice a week for 5 weeks significantly increased the expression level of Cyp 3a11 in the liver of mice and the mRNA level of Cyp 1a1 in the intestine [6]. Intraperitoneal injection of a 3mg/kg dose of Ivermectin every other day for 30 days, which significantly inhibited tumor growth in the ovarian cancer xenograft mouse model, without affecting the body weight of the mice[7].
References:
[1] Dourmishev, Assen L., Lyubomir A. Dourmishev, and Robert A. Schwartz. "Ivermectin: pharmacology and application in dermatology." International journal of dermatology 44.12 (2005): 981-988.
[2] Crump A. Ivermectin: enigmatic multifaceted ‘wonder’drug continues to surprise and exceed expectations[J]. The Journal of antibiotics, 2017, 70(5): 495-505.
[3] Johnson-Arbor K. Ivermectin: a mini-review[J]. Clinical Toxicology, 2022, 60(5): 571-575.
[4] Song D, Liang H, Qu B, et al. Ivermectin inhibits the growth of glioma cells by inducing cell cycle arrest and apoptosis in vitro and in vivo[J]. Journal of Cellular Biochemistry, 2019, 120(1): 622-633.
[5] Lv C, Liu W, Wang B, et al. Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo[J]. Antiviral research, 2018, 159: 55-62.
[6] Albérich M, Ménez C, Sutra J F, et al. Ivermectin exposure leads to up-regulation of detoxification genes in vitro and in vivo in mice[J]. European journal of pharmacology, 2014, 740: 428-435.
[7] Zhang X, Qin T, Zhu Z, et al. Ivermectin augments the in vitro and in vivo efficacy of cisplatin in epithelial ovarian cancer by suppressing Akt/mTOR signaling[J]. The American journal of the medical sciences, 2020, 359(2): 123-129.
Ivermectin是一种大环内酯类内外抗寄生虫药，对体内和体外寄生虫均有活性[1]。Ivermectin可破坏神经和肌肉细胞中的神经传递，引起神经元膜超极化，诱导体肌（尤其是咽泵）麻痹，从而杀死寄生虫[2]。Ivermectin已被广泛用于抑制寄生虫感染和杀灭病毒[3]。
在体外，Ivermectin处理48小时显著抑制了C6细胞和U251细胞的增殖，IC50值分别为16.32µM和14.58µM[4]。2.5µM的Ivermectin处理BHK-21细胞72小时，降低了c(PRV)的增殖，并抑制了PRV DNA聚合酶辅助亚基UL42进入细胞核[5]。
在体内，每周两次口服0.2mg/kg剂量的Ivermectin，持续5周，显著增加了小鼠肝脏中Cyp 3a11的表达水平以及肠道中Cyp 1a1的mRNA水平[6]。每隔一天腹腔注射3mg/kg剂量的Ivermectin，持续30天，显著抑制了卵巢癌异种移植小鼠模型中的肿瘤生长，且未影响小鼠的体重[7]。