Emamectin is a non-selective allosteric activator of nicotinic acetylcholine receptors and GABAA/C receptors

Avermectins are a group of compounds isolated from a soil-dwelling bacterium. They have been widely used as parasiticides and insecticides, acting by relatively irreversible activation of invertebrate chloride channels. Emamectin is a soluble derivative of an avermectin. It is an insecticide, which persistently activates glutamate-gated chloride channels. However, its effects on mammalian ligand-gated ion channels are unknown. To this end, we tested the effect of emamectin on two cation selective nicotinic receptors and two GABA-gated chloride channels expressed in Xenopus oocytes using two-electrode voltage clamp. Our results demonstrate that emamectin could directly activate alpha 7 nAChR, alpha 4 beta 2 nAChR, alpha 1 beta 2 gamma 2 GABA(A) receptor and rho 1 GABA(C) receptor concentration dependently, with similar potencies for each channel. However, the potencies for it to activate these channels were at least two orders of magnitude lower than its potency of activating invertebrate glutamate-gated chloride channel. In contrast, ivermectin only activated the alpha 1 beta 2 gamma 2 GABA(A) receptor. (C) 2016 Elsevier Inc. All rights reserved.