Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland.
Parasitology. 2012 Jun;139(7):934-44. doi: 10.1017/S0031182012000066. Epub 2012 Feb 6.
Miltefosine was investigated for its activity against Neospora caninum tachyzoites in vitro, and was shown to inhibit the proliferation of N. caninum tachyzoites cultured in human foreskin fibroblasts (HFF) with an IC50 of 5·2 μM. Treatment of infected cells with 25 μM miltefosine for a period of 10 h had only a parasitostatic effect, while after 20 h of treatment parasiticidal effects were observed. This was confirmed by transmission electron microscopy of N. caninum-infected and miltefosine-treated HFF. Administration of miltefosine to N. caninum-infected Balb/c female mice at 40 mg/kg/day for 14 days resulted in 6 out of 10 mice exhibiting weight loss, ruffled coat and apathy between days 7 and 13 post-infection. In the group that received placebo, only 2 out of 8 mice succumbed to infection, but the cerebral burden was significantly higher compared to the miltefosine treatment group. In a second experiment, the time-span of treatment was reduced to 5 days, and mice were maintained without further treatment for 4 weeks. Only 2 out of 9 mice in the miltefosine treatment group exhibited signs of disease, while 8 out of 10 mice succumbed to infection in the placebo group. These results showed that miltefosine hampered the dissemination of parasites into the CNS during experimental N. caninum infection in mice.
米替福新被研究用于抗体外的刚地弓形虫速殖子，结果表明其对在人包皮成纤维细胞（HFF）中培养的刚地弓形虫速殖子的增殖具有抑制作用，IC50 为 5.2 μM。用 25 μM 米替福新处理感染细胞 10 小时仅具有抑菌作用，而处理 20 小时则观察到杀寄生虫作用。这通过刚地弓形虫感染和米替福新处理的 HFF 的透射电子显微镜得到证实。在感染 40 天的 Balb/c 雌性小鼠中以 40 mg/kg/天的剂量给予米替福新，在感染后第 7 至 13 天，有 10 只小鼠中的 6 只出现体重减轻、毛发蓬乱和冷漠。在接受安慰剂的组中，只有 8 只中的 2 只感染死亡，但与米替福新治疗组相比，脑负荷显著更高。在第二个实验中，将治疗时间缩短至 5 天，并且在没有进一步治疗的情况下将小鼠维持 4 周。在米替福新治疗组中，只有 9 只小鼠中的 2 只出现疾病迹象，而在安慰剂组中，有 10 只中的 8 只感染死亡。这些结果表明，米替福新阻碍了寄生虫在实验性刚地弓形虫感染的小鼠中向中枢神经系统的传播。
