Mechanisms of action of emodepside

Parasitol Res. 2005 Oct:97 Suppl 1:S1-S10. doi: 10.1007/s00436-005-1438-z.

Abstract

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.

MeSH terms

  • Animals
  • Anthelmintics / chemistry*
  • Anthelmintics / pharmacology*
  • Cattle
  • Cattle Diseases / drug therapy
  • Cattle Diseases / parasitology
  • Depsipeptides / chemistry*
  • Depsipeptides / pharmacology*
  • Drug Resistance
  • Molecular Structure
  • Nematoda / drug effects
  • Nematoda / genetics
  • Nematode Infections / drug therapy
  • Nematode Infections / veterinary
  • Phylogeny
  • Plant Leaves
  • Sheep
  • Sheep Diseases / drug therapy
  • Sheep Diseases / parasitology

Substances

  • Anthelmintics
  • Depsipeptides
  • emodepside