Ivermectin Interactions with Invertebrate Ion Channels

Ivermectin is a semi-synthetic analog of avermectin B1a. It is a potent anthelmintic/insecticide effective against a broad range of parasites. Ivermectin binding sites from nematodes and insects have been characterized by employing a 3Hivermectin binding assay and subsequently identified with an 125I-azido-avermectin analog. Avermectin binding proteins from the free living nematode, Caenorhabditis elegans, and from the dipteran, Drosophila melanogaster, have been purified by immuno-affinity chromatography using a monoclonal antibody against the ligand, avermectin. Electrophysiological and pharmacological characterization of the chloride ion channel target of ivermectin action in C. elegans has been accomplished by injecting C. elegans mRNA into Xenopus oocytes and studying the expressed chloride ion channel. The endogenous ligand for the avermectin sensitive chloride channel expressed in oocytes is glutamate. At low concentrations, ivermectin potentiates the effect of glutamate on the channel, while at high concentrations, ivermectin causes irreversible opening of the channel.