Avermectin and avermectin derivatives are antagonists at the 4-aminobutyric acid (GABA) receptor on the somatic muscle cells of Ascaris; is this the site of anthelmintic action?

The mechanism underlying the ability of the anthelmintic avermectin to paralyse the nematode Ascaris is not yet fully understood. Using conventional two-electrode electrophysiological recording techniques we have demonstrated that micromolar concentrations of ivermectin block the inhibitory GABA response on the muscle cells of the parasitic nematode Ascaris. The ability of a number of avermectin derivatives to act as receptor antagonists for the Ascaris muscle GABA receptor has been determined. This provides useful information to compare with the in vivo anthelmintic potency of these compounds. Abamectin, the most potent anthelmintic, was the most potent compound at inhibiting the GABA response whilst octahydroavermectin, a compound which lacks anthelmintic activity, did not block the GABA receptor. This is consistent with the notion that the GABA receptor antagonist properties of the avermectins could contribute to their anthelmintic action.