Cyclic Octadepsipeptides

Research on the cyclic octadepsipeptides begin in the early 1990s. PF1022A, the parent compound of emodepside, is a natural secondary metabolite of the fungus Mycelia sterilia. Emodepside is a semisynthetic derivative of PF1022A and is effective against a variety of GI nematodes. The current understanding of the mode of action of emodepside is that it binds to a presynaptic latrophilin receptor in nematodes. Recent findings indicate that a second emodepside target is the calcium-activated potassium channel SL01. Interaction with these receptors leads to a flaccid paralysis of the pharynx and the somatic musculature in nematodes. Emodepside is currently available in some countries in combination with praziquantel (for treatment of cestode infections) as topical formulation (3 mg/kg) for the treatment of ascarids and hookworms in cats.

Amino-acetonitrile Derivatives (AAD)

AAD are a class of low-molecular, mass compounds bearing different aryloxy and aroyl moieties on an amino-acetonitrile core. AAD have been found to express anthelmintic activity. They are a class of synthetic compounds with high activity against GI nematodes, including isolates resistant to the commercially available broad-spectrum anthelmintic classes, due to a novel mode of action. AAD interfere with a unique ACR23 nicotinic acetylcholine receptor subunit which belongs to the DEG-3 nematode-specific subfamily. Efficacy studies have shown that monepantel (2.5 mg/kg, PO) effectively controls adult and L4 stages of ruminant nematodes, including strains that are resistant to the other currently available broad-spectrum anthelmintic classes. Monepantel drench is currently registered for use in sheep in New Zealand.

Last full review/revision March 2012 by Edwin Claerebout, DVM, PhD, DEVPC; Jozef Vercruysse, DVM, DEVPC