Emodepside and SL0-1 potassium channels: A review

• Published in: Experimental parasitology 2012-09, Vol.132 (1), p.40-46
• Main Authors: Martin, R.J., Buxton, S.K., Neveu, C., Charvet, C.L., Robertson, A.P.
• Format: Article
• Language: English
• Subjects: agonists; Animals; anthelmintics; Anthelmintics - pharmacology; Anthelmintics - therapeutic use; Ascaris suum; benzimidazoles; Caenorhabditis elegans; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - metabolism; Caenorhabditis elegans - physiology; Depsipeptides - pharmacology; Depsipeptides - therapeutic use; domestic animals; Drug Resistance; drugs; Emodepside; gastrointestinal nematodes; Humans; lactones; Large-Conductance Calcium-Activated Potassium Channels - drug effects; Large-Conductance Calcium-Activated Potassium Channels - metabolism; Life Sciences; lungworms; mechanism of action; Membrane Potentials - drug effects; Membrane Potentials - physiology; Microbiology and Parasitology; Muscle Contraction - drug effects; Muscle Contraction - physiology; muscles; Nematoda; Nematoda - drug effects; Nematoda - metabolism; Nematoda - physiology; Nematode Infections - drug therapy; Nematode Infections - parasitology; Nematode Infections - prevention & control; Neuromuscular Junction - drug effects; Neuromuscular Junction - metabolism; Neuropeptides - metabolism; Parasitology; potassium; potassium channels; Receptors, Peptide - drug effects; Receptors, Peptide - metabolism; sanitation; SLO-1; vaccination; Voltage-activated potassium currents
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2011.08.012

[Display omitted] . ► Emodepside is a broad spectrum cyclooctadepsipeptide anthelmintic drug. ► It has a mode of action different from the other classical groups of anthelmintics. ► We review its mode of action that show it inhibits neuronal and muscle activity. ► Rescue experiments suggest emodepside opens nematode Ca-dependent SLO-1 K channels. ► Its slow time-dependent action suggests it does not act in the extracellular domain of these channel. Nematode parasites infect humans and domestic animals; treatment and prophylaxis require anthelmintic drugs because vaccination and sanitation is limited. Emodepside is a more recently introduced cyclooctadepsipeptide drug that has actions against GI nematodes, lungworm, and microfilaria. It has a novel mode of action which breaks resistance to the classical anthelmintics (benzimidazoles, macrocyclic lactones and cholinergic agonists). Here we review studies on its mode of action which suggest that it acts to inhibit neuronal and muscle activity of nematodes by increasing the opening of calcium-activated potassium (SLO-1) channels.