Emodepside is a novel cyclo-octadepsipeptide that paralyses nematodes (1). A number of different lines of evidence indicated that the effect of emodepside may involve an effect on neurotransmitter release including the following: it causes de-staining of neurones labelled with FM4-64;
goa-1(
n1134) and
egl-30(
tg26), both of which are predicted to have increased ACh release at the neuromuscular junction, are hypersensitive to emodepside in two assays, locomotion and pharyngeal pumping; strains with mutations in various synaptic proteins involved in vesicular-mediated release of neurotransmitter are less susceptible to the paralytic actions of emodepside (2).. A mutagenesis screen has been performed to isolate highly resistant animals. These resistant animals show at least a hundred-fold less sensitivity to emodepside than wild-type and intriguingly show hyper-sensitivity to the acetylcholine esterase inhibitor aldicarb. This suggests that emodepside may reduce acetylcholine release at the neuromuscular junction, in contrast to the previous model of increased transmitter release. Aldicarb is being used as a tool to address the effects of emodepside on acetylcholine release and to resolve these conflicting results. Recent data indicate that treatment of wild-type animals with a low concentration of emodepside increases the time to paralysis in the presence of aldicarb. Currently we are testing whether sensitivity to levamisole is also affected by pretreatment with emodepside.. (1) Harder et al., 2005 Parasitol Res 97, S1-S10. (2) Willson et al., 2004 Current Biology 14, 1374-1379. Supported by BBSRC CASE and Bayer. We are grateful to the C. elegans knockout consortium (USA and Japan) for the provision of strains.