1. Academic Validation
  2. Mechanisms of action of emodepside

Mechanisms of action of emodepside

  • Parasitol Res. 2005 Oct;97 Suppl 1:S1-S10. doi: 10.1007/s00436-005-1438-z.
A Harder 1 L Holden-Dye 2 R Walker 3 F Wunderlich 3
Affiliations

Affiliations

  • 1 Bayer HealthCare AG, Animal Health Division, Research and Development, Parasiticides, 51368, Leverkusen, Germany. achim.harder@bayerhealthcare.com.
  • 2 Southampton Neuroscience Group, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.
  • 3 Division of Molecular Parasitology and Centre for Biological and Medical Research, Heinrich-Heine-University, 40225, Düsseldorf, Germany.
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.

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