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

Abstract

The mechanism underlying the ability of the anthelmintic avermectin to paralyse the nematodeAscarisis 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 nematodeAscaris. The ability of a number of avermectin derivatives to act as receptor antagonists for theAscarismuscle GABA receptor has been determined. This provides useful information to compare with thein vivoanthelmintic 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.