Background & objectives: Pentavalent antimonials are the standard treatment for cutaneous leishmaniasis (CL), however, treatment failures are frequent. Nimodipine, a calcium channel blocker is known to show promising antiprotozoal effects. Here, we investigated the antileishmanial effect of Nimodipine in both in vitro and in vivo BALB/c mice model of CL. We also compared the in vivo effect with amphotericin B and meglumine antimoniate in the experimental CL mice model.
Methods: Colorimetric alamar blue assay and J774 A.1 mouse macrophage cells were used to determine the effect of nimodipine on promastigotes and amastigotes viability, respectively. Then, the in vivo activity of nimodipine was compared to that of conventional therapies in both the early and established courses of Leishmania major infection in susceptible non-healing BALB/c mice.
Results: Nimodipine was highly active against promastigotes and amastigotes of L. major with IC₅₀ values of 49.40 and 15.03 μM, respectively. In the early model, the combination therapy with meglumine antimoniate and nimodipine showed no parasites in the spleen or footpad of animals. The footpad thickness was significantly lower in mice treated with either nimodipine (1 mg/kg or 2.5 mg/kg) or amphotericin B compared to the control group in the established lesions model. However, no complete remission was observed in the footpad lesion of any of the treatment groups (nimodipine, amphotericin B, meglumine antimoniate, and combination therapy).
Interpretation & conclusion: The effect of nimodipine was comparable to that of amphotericin B and meglumine antimoniate in early and established CL lesion models. Since nimodipine is more cost-effective than conventional therapies, our results merit further investigation in other animal models and voluntary human subjects.

中文翻译：

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尼莫地平在敏感 BALB/c 小鼠体内体外和体内抗利什曼原虫活性的研究

背景与目的：五价锑是皮肤利什曼病 (CL) 的标准治疗方法，但治疗失败的情况屡见不鲜。众所周知，尼莫地平是一种钙通道阻滞剂，显示出有希望的抗原虫作用。在这里，我们研究了尼莫地平在CL 的体外和体内BALB/c 小鼠模型中的抗利什曼原虫作用。我们还在实验性 CL 小鼠模型中比较了两性霉素 B 和葡甲胺锑酸盐的体内作用。
方法：采用比色法阿拉玛蓝法和J774 A.1小鼠巨噬细胞分别测定尼莫地平对前鞭毛体和无鞭毛体活力的影响。那么，体内尼莫地平的活性在易感的非愈合 BALB/c 小鼠的利什曼原虫主要感染的早期和已建立的过程中与常规疗法的活性进行了比较。
结果：尼莫地平对L. Major 的前鞭毛体和无鞭毛体具有高度活性，IC ₅₀值分别为 49.40 和 15.03 μM。在早期模型中，葡甲胺锑酸盐和尼莫地平的联合治疗显示动物的脾脏或足垫中没有寄生虫。在建立的病变模型中，与对照组相比，用尼莫地平（1 mg/kg 或 2.5 mg/kg）或两性霉素 B 治疗的小鼠的足垫厚度显着降低。然而，在任何治疗组（尼莫地平、两性霉素 B、葡甲胺锑酸盐和联合治疗）的足垫病变中均未观察到完全缓解。
解读与结论：在早期和已建立的 CL 病变模型中，尼莫地平的作用与两性霉素 B 和葡甲胺锑酸盐的作用相当。由于尼莫地平比传统疗法更具成本效益，我们的结果值得在其他动物模型和自愿人类受试者中进一步研究。