Ivermectin

Ivermectin is a multifaceted drug, primarily known for its role in treating parasitic infections. Discovered in the late 1970s, it has been a cornerstone in veterinary and human medicine, particularly for diseases like river blindness and elephantiasis. Its discovery was so significant that it led to the awarding of the Nobel Prize in Physiology or Medicine to Satoshi Ōmura and William C. Campbell in 201547. Beyond its antiparasitic applications, recent research has uncovered potential anticancer properties, making ivermectin a subject of renewed scientific interest146.

Ivermectin operates through several mechanisms depending on the target organism and cell type. In parasitic nematodes and insects, it is known to enhance the activity of glutamate-gated chloride channels, leading to paralysis and death of the parasite79. This action is selective for invertebrates, which is why ivermectin is safe for human use3. In cancer cells, ivermectin has been shown to induce cytostatic autophagy by inhibiting the PAK1/Akt/mTOR signaling pathway, leading to decreased proliferation and tumor growth1. Additionally, ivermectin modulates other ion channels and receptors, such as P2X4 receptor channels, Cys-loop receptors, and G-protein-gated inwardly rectifying K+ (GIRK) channels, which may contribute to its therapeutic effects2510.

Antiparasitic Applications

Ivermectin's primary application has been in the treatment of parasitic infections. It has been used to combat onchocerciasis and lymphatic filariasis with great success, significantly improving human health and welfare in affected regions47. Its mode of action against parasites involves the modulation of glutamate-gated chloride channels, which are crucial for the function of these organisms9.

Anticancer Applications

Recent studies have highlighted ivermectin's potential as an anticancer agent. It has been reported to inhibit the proliferation of various tumor cells by regulating multiple signaling pathways and inducing programmed cell death46. For instance, in breast cancer, ivermectin activates cytostatic autophagy, which suppresses tumor growth1. The drug's ability to induce cell death through different mechanisms, such as caspase-dependent apoptosis and immunogenic cell death, opens new avenues for cancer therapy6.

Modulation of Ion Channels and Receptors

Ivermectin's interaction with ion channels and receptors extends beyond its antiparasitic effects. It has been shown to facilitate human P2X4 receptor channels, which play a role in pain and inflammation2. Additionally, ivermectin activates GIRK channels in a phosphatidylinositol-4,5-biphosphate-dependent manner, which could have implications for neurological disorders10. The drug's ability to target various ligand-gated ion channels and receptors suggests potential applications in treating a wide range of human neurological disorders35.

Repositioning for Other Diseases

Beyond its established uses, there is ongoing research into repositioning ivermectin for the treatment of diseases not caused by helminth and insect parasites. Preliminary studies have shown antiviral, antimalarial, antimetabolic, and anticancer effects in tissue culture at concentrations higher than those used for anthelmintic purposes9. However, caution is advised when extrapolating these findings to clinical use, particularly for emerging diseases like Covid-19, due to the high concentrations required in vitro9.