Mebendazole

Mebendazole is a highly effective, broad-spectrum antihelmintic indicated for the treatment of nematode infestations; has been found as a hedgehog inhibitor.

References:
[1]. Liu C, et al. In vivo and in vitro efficacies of mebendazole, mefloquine and nitazoxanide against cyst echinococcosis. Parasitol Res. 2015 Mar 15. [2]. Pawluk SA, et al. A review of pharmacokinetic drug-drug interactions with the anthelmintic medications albendazole and mebendazole. Clin Pharmacokinet. 2015 Apr;54(4):371-83. [3]. Speich B, et al. Efficacy and safety of albendazole plus ivermectin, albendazole plus mebendazole, albendazole plus oxantel pamoate, and mebendazole alone against Trichuris trichiura and concomitant soil-transmitted helminth infections: a four-arm, random [4]. Larsen AR, et al. Repurposing the antihelmintic mebendazole as a hedgehog inhibitor. Mol Cancer Ther. 2015 Jan;14(1):3-13.

Effectiveness and Tolerability of 3-Day Mebendazole Treatment of Giardia duodenalis Infection in Adults and Children: Two Prospective, Open-Label Phase IV Trials.[Pubmed:30792825]

Curr Ther Res Clin Exp. 2018 Nov 30;89:43-47.

Background: Giardia duodenalis is the most common intestinal pathogenic protozoan infection reported in humans. Both in vitro studies and 4 separate, sequential, comparative clinical trials conducted by our group in Cuba demonstrated Mebendazole activity against G. duodenalis infection in both children and adults. Objective: The 2 additional, prospective, open-label, Phase IV follow-up studies reported here were performed to further assess the effectiveness and safety profile of Mebendazole in the outpatient treatment of G. duodenalis infection. Methods: Assenting children (n=522) whose guardians gave permission and consenting adults (n=423) diagnosed with G. duodenalis infection were given Mebendazole (200 mg 3 times daily for 3 days). Medical histories and stool samples were obtained and physical/laboratory examinations were performed pretreatment then repeated on days 3, 5, and 7 after treatment completion. The evaluation of efficacy (ie, cure) was based on parasitologic response to therapy. Participants were considered cured, if no Giardia trophozoites or cysts were found in any of the 3 posttreatment fecal specimens evaluated by direct wet mounts and/or after Ritchie concentration techniques. Results: No participant refused to be enrolled and all returned for follow-up examinations. At the end of the treatment, stool samples were negative in 450 out of 522 children (86.2%) and 392 of 423 adults (92.7%). Treatment was well tolerated. In adults, the only adverse effect reported was abdominal pain (6.2%). Side effects reported in children included abdominal pain (5.6%), nausea (2.9%), and vomiting (2.3%). Reported side effects were all mild, transient, and self-limited and did not require discontinuation of treatment or additional medication. Conclusions: Mebendazole may be an effective alternative treatment of G. duodenalis infections in both children and adults.

Autophagy Is a Potential Target for Enhancing the Anti-Angiogenic Effect of Mebendazole in Endothelial Cells.[Pubmed:30642153]

Biomol Ther (Seoul). 2019 Jan 1;27(1):117-125.

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.

Mebendazole is a highly effective, broad-spectrum antihelmintic indicated for the treatment of nematode infestations; has been found as a hedgehog inhibitor.

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