Emodepside is an anthelmintic drug that is effective against a number of gastrointestinal nematodes, is licensed for use in cats and belongs to the class of drugs known as the octadepsipeptides, a relatively new class of anthelmintic (research into these compounds began in the early 1990s), which are suspected to achieve their anti-parasitic effect by a novel mechanism of action due to their ability to kill nematodes resistant to other anthelmintics. Synthesis Emodepside is synthesised by attaching a morpholine ring “at the paraposition of each of the two D-phenyllactic acids” to PF1022A, a metabolite of Mycelia sterile, a fungus that inhabits the leaves of Camellia japonica – a flowering shrub. Anthelmintic effects When applied to nematodes, emodepside has been shown to have a range of effects, inhibiting muscle in the parasitic nematode Ascaris sum, and inhibiting locomotive and pharyngeal movement in Caenorhabditis elegans in addition to having effects in other tissues such as the inhibition of egg laying. Mechanism of action One of the ways in which this drug achieves its effects has been shown to be through binding to a group of G-protein coupled receptors called latrophilins, first identified as being target proteins for α-latrotoxin (the other target protein of α-LTX being neurexin, a membrane receptor with laminin-like extracellular domains), a component of black widow spider venom that can cause paralysis and subsequent death in nematodes and humans alike. LAT-1 (1014 amino acids, 113 KDa coded by the B0457.1 gene) and LAT-2 (1338 amino acids, 147 KDa coded by the B0286.2 gene) are located presynaptically at the neuromuscular junction in Caenorhabditis elegans and share 21% amino acid identity with each other (the amino acid sequence homology LAT-1 shares with rat, bovine and human latrophilins has been shown to be 22, 23 and 21% respectively). Following receptor-ligand binding, a conformational change induced in the receptor activates the Gq protein, freeing the Gqα subunit from the βγ complex. The Gqα protein then goes on to couple-to and activate the signaling molecule phospholipase-C-β, a protein that has been identified as being key to the modulation of regulatory pathways of vesicle release in C.elegans. In its signaling cascade, PLC-β (like other phospholipases) hydrolyses phosphatidylinositolbisphosphate to yield inositol trisphosphate (IP3) and diacylglycerol (DAG). As IP3 receptors have sparse or little distribution throughout the pharyngeal nervous system of C.elegans (one of the tissues where LAT-1 agonists such as α-LTX and emodepside have their most predominant