Emodepside, a cyclo-octadepsipeptide anthelmintic with a novel mode of action

Abstract

Due to the development of drug resistance, there is a continual need for new anthelmintics with novel modes of action. Emodepside, a cyclo-octadepsipeptide, was originally thought to modify GABAergic transmission in parasitic nematodes. However, more recent studies using the parasitic nematode Ascaris suum and the free-living nematode Caenorhabditis elegans indicate that emodepside interacts with a presynaptic latrophilin receptor to release a transmitter or modulator. This presynaptic signaling pathway involves activation of a Gaq protein and phospholipase-?, which mobilizes diacylglycerol (DAG). DAG activates UNC-13, which in turn activates synaptobrevin to increase release of the transmitter or modulator. The released transmitter or modulator acts postsynaptically to modify pharyngeal and somatic body wall muscle activity.