Ivermectin and its target molecules: shared and unique modulation mechanisms of ion channels and receptors by ivermectin

 The IVM‐binding site in Cys‐loop receptors and the farnesoid X receptor (FXR), and the predicted IVM‐binding site in the P2X₄ receptor and the G‐protein‐gated inwardly rectifying K⁺ (GIRK) channel.

Abstract

Ivermectin (IVM) is an antiparasitic drug that is used worldwide and rescues hundreds of millions of people from onchocerciasis and lymphatic filariasis. It was discovered by Satoshi Ōmura and William C. Campbell, to whom the 2015 Nobel Prize in Physiology or Medicine was awarded. It kills parasites by activating glutamate‐gated Cl⁻ channels, and it also targets several ligand‐gated ion channels and receptors, including Cys‐loop receptors, P2X₄ receptors and fernesoid X receptors. Recently, we found that IVM also activates a novel target, the G‐protein‐gated inwardly rectifying K⁺ channel, and also identified the structural determinant for the activation. In this review, we aim to provide an update and summary of recent progress in the identification of IVM targets, as well as their modulation mechanisms, through molecular structures, chimeras and site‐directed mutagenesis, and molecular docking and modelling studies.

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