Research reportExpression of a glutamate-activated chloride current in Xenopus oocytes injected with Caenorhabditis elegans RNA: evidence for modulation by avermectin
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Advances in our understanding of nematode ion channels as potential anthelmintic targets
2022, International Journal for Parasitology: Drugs and Drug ResistanceIvermectin represses Wnt/β-catenin signaling by binding to TELO2, a regulator of phosphatidylinositol 3-kinase-related kinases
2022, iScienceCitation Excerpt :In addition to its approved uses, IVM is expected to be effective against viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Caly et al., 2020; Heidary and Gharebaghi, 2020), and various cancers (Tang et al., 2021). IVM binds to glutamate-gated chloride channels and potentiates them in the nerve and muscle cells of parasites, causing neuronal hyperpolarization, inducing muscle paralysis, and subsequently killing the parasites (Arena et al., 1992; Cully et al., 1994). In contrast, to our knowledge, the direct targeting of other biological activities in viruses and mammals by IVM has not been reported.
The avermectin/milbemycin receptors of parasitic nematodes
2022, Pesticide Biochemistry and PhysiologyCitation Excerpt :Though ivermectin is the sole member of the family currently licensed for use in humans – moxidectin is in phase 3 clinical trials (Milton et al., 2020) – a number of other drugs have been developed and licensed for use in animal health, including moxidectin, doramectin, abamectin, milbemycin oxime and selamectin. It quickly became apparent that ivermectin acts on the nematode nervous system, and researchers at Merck identified glutamate-gated chloride channels (GluCls) as the ivermectin target in the free-living nematode, Caenorhabditis elegans (Arena et al., 1992), having first demonstrated the existence of a specific high-affinity binding site (Cully and Paress, 1991). Shortly afterwards, Cully et al. (1994) identified two cDNA clones that, when expressed together in Xenopus oocytes, produced GluCls which were potentiated by low concentrations of ivermectin.
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2022, New Aspects of Meat Quality: From Genes to Ethics, Second EditionHeartworm disease – Overview, intervention, and industry perspective
2021, International Journal for Parasitology: Drugs and Drug ResistanceA perspective on the discovery of selected compounds with anthelmintic activity against the barber's pole worm—Where to from here?
2020, Advances in ParasitologyCitation Excerpt :Indeed, there are few anthelmintics targeting the energy production system in nematodes; indeed, most currently used drugs target the nematode neuromuscular system (Holden-Dye and Walker, 2014; Kotze, 2012). For instance, imidazothiazoles act as cholinergic agonists at nicotinic neuromuscular junctions (Coles et al., 1975; McKellar and Jackson, 2004; Prichard, 1990), macrocyclic lactones target neurotransmitter gamma-aminobutyric acid-gated chloride ion channels and glutamate-gated chloride ion channels (Arena et al., 1992; Brownlee et al., 1997), monepantel binds to nicotinic acetylcholine receptor subunits (Baur et al., 2015; Kaminsky et al., 2008a; Sargison, 2012) and derquantel represents nicotinic acetylcholine receptor antagonists (Ruiz-Lancheros et al., 2011; Sargison, 2012). Here, tolfenpyrad shows some promise as a new anthelmintic compound, but needs to be critically explored further, optimised and rigorously re-assessed for safety and efficacy in vivo in animals.