Mechanisms of action of emodepside.
The research of the class of cyclic octadepsipeptides started at the beginning of the 1990s. PF1022A, the starting material of emodepside, is a natural secondary metabolite of the fungus Mycelia sterilia, which belongs to the microflora of the leaves of Camellia japonica. PF1022A consists of four N-methyl-L-leucins, two D-Iactic acids and two D-phenyllactic acids, which build up a cyclic octadepsipeptide with an alternating L-D-L-configuration. Emodepside is a semisynthetic derivative of PF1022A, which contains a morpholine attached in para position at each of both D-phenyllactic acids. Emodepside is efficacious against a variety of gastrointestinal nematodes. Emodepside binds to a presynaptic latrophilin receptor in nematodes. The following presynaptic signal transduction occurs via activation of Gqalpha protein and phospholipase-Cbeta, which leads to mobilization of diacylglycerol (DAG). DAG then activates UNC-13 and synaptobrevin, two proteins which play an important role in presynaptic vesicle-functioning. This finally leads to the release of a currently unidentified transmitter. The transmitter (or modulator) exerts its effects at the postsynaptic membrane and induces a flaccid paralysis of the pharynx and the somatic musculature in nematodes.
Harder
A
A
Bayer HealthCare AG, Animal Health Division, Research and Development, Parasiticides, 51368, Leverkusen, Germany. achim.harder@bayerhealthcare.com.
Holden-Dye
L
L
Southampton Neuroscience Group, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.
Walker
R
R
Division of Molecular Parasitology and Centre for Biological and Medical Research, Heinrich-Heine-University, 40225, Düsseldorf, Germany.
Wunderlich
F
F
Division of Molecular Parasitology and Centre for Biological and Medical Research, Heinrich-Heine-University, 40225, Düsseldorf, Germany.
D000818:Animals; D000871:Anthelmintics / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy / Q000469:parasitology; D047630:Depsipeptides / Q000737:chemistry* / Q000494:pharmacology*; D004351:Drug Resistance; D015394:Molecular Structure; D009348:Nematoda / Q000187:drug effects / Q000235:genetics; D009349:Nematode Infections / Q000188:drug therapy / Q000662:veterinary; D010802:Phylogeny; D018515:Plant Leaves; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy / Q000469:parasitology
D000871:Anthelmintics; D047630:Depsipeptides; C468987:emodepside