(A) Isometric contraction of Ascaris suum muscle strips produced by application of increasing concentrations of acetylcholine and antagonism by 1 μM derquantel (red bar), 1 μM derquantel + 0.3 μM abamectin (green bar), and wash (gray bar). Note that derquantel decreases the responses to acetylcholine and that the addition of abamectin increases the inhibition. (B) An A. suum muscle strip concentration–contraction–response plot of acetylcholine showing mean ± S.E. bars (n = 11). Control (black); in the presence of 1 μM derquantel (red); 1 μM derquantel + 0.3 μM abamectin (green); and wash (blue). Note that abamectin increases the inhibition produced by derquantel. The inhibitory effect of abamectin and derquantel is greater than an additive effect, dotted line [37]. (C) Model of ligand sites of action showing complex effects on heteromeric ion channels. The cholinergic anthelmintic agonists bind to the orthosteric sites, opening the channel. Low concentrations of abamectin (0.03 and 0.1 μM) bind to a negative allosteric site (NAM) in the lipid phase of the channel, inhibiting opening. Higher concentrations of abamectin (0.3, 1, and 10 μM) bind to a positive allosteric site (PAM), increasing opening [35].