Actions of imidacloprid and a related nitromethylene on cholinergic receptors of an identified insect motor neurone

Abstract

Nitromethylenes and their analogues are a novel class of insecticidally active molecules of commercial importance. Here we describe the actions of a novel nitroguanidine analogue, l‐(6‐chloro‐3‐pyridylmethyl)‐N‐nitroimidazolidin‐2‐ylideneamine (imidacloprid; NTN 33893) and a nitromethylene, l‐(3‐pyridylmethyl)‐2‐nitromethylene‐imidazolidine (PMNI) on the cockroach fast coxal depressor motor neurone Df and their effectiveness in displacing [125I]α‐bungarotoxin binding to cockroach nerve cord preparations. When tested on the cell body of this identified neurone both imidacloprid and PMNI induce slow depolarizations, which are sensitive to nicotinic receptor antagonists, such as dihydro‐β‐erythroidine (1.0 × 10−5 M) and mecamylamine (1.0 × 10−4 M). Lower concentrations of imidacloprid (1.0 × 10−8 −1.0 × 10−6 M) and PMNI (1.0 × 10−8 M) show no antagonist action on nicotine‐induced depolarization. At concentrations in the range 1.0 × 10−7 −5.0 × 10−7 M, PMNI partially and reversibly blocks nicotine‐induced depolarization. Both compounds are more effective displacers of specific [125I]α‐bungarotoxin binding than nicotine, with imidacloprid (IC50 = 2.0 × 10−7 M) about tenfold more potent than PMNI (IC50 = 1.3 × 10−6 M).

Temperature‐Sensitive Expression of Drosophila Neuronal Nicotinic Acetylcholine Receptors

“…In the insect nervous system, ACh appears to be the principal excitatory neurotransmitter (Pitman, 1971), and nAChRs are present in high densities in insect neural membrane extracts (Sattelle, 1980;Breer and Sattelle, 1987). Insect neuronal nAChRs are also an important site of action of insecticides such as nitromethylenes and nitroguanidines (Sattelle et al, 1989;Bai et al, 1991;Zwart et al, 1994;Buckingham et al, 1995;Tomizawa et al, 1996). characterization.…”

The invertebrate pharmacology of insecticides acting at nicotinic acetylcholine receptors

“…Additionally, given the increasing chemical diversity of orthosteric modulators we identify updated criteria for defining the neonicotinoids as originally introduced by Yamamoto,37) specifically in relation to mode of action. [58][59][60] The commercial chloropyridyl neonicotinoids all displace [ 3 H]-IMI binding with high potency (low nM K i ), implying that chloropyridyl neonicotinoids share common nAChR target(s) site(s). The non-chloropyridyl neonicotinoids vary in their pharmacological profile with respect to IMI and are discussed in subsequent sections.…”

Chemical Compatibility and Safety of Imidacloprid/Flumethrin Collar (Seresto®) Concomitantly Used with Imidacloprid/Moxidectin (Advocate®, Advantage® Multi) and Emodepside/Praziquantel (Profender®) Spot-on Formulations

“…Imidacloprid was registered in Europe in 1997 for use as a veterinary medicinal product in cats and dogs, while flumethrin was registered in Europe even earlier in 1986 for use as a veterinary medicinal product for companion and food producing animals. Imidacloprid is a neonicotinoid insecticide which acts as a strong agonist at nicotinic acetylcholine receptors (nAChRs) on the post-synaptic membrane, causing sustained depolarization of the neuron and death of the flea or louse (Bai et al 1991). Imidacloprid is highly selective for insect nAChRs, to which it binds up to 1,000 times more strongly than to mammalian nAChRs, so it exhibits extremely low mammalian and environmental toxicity (Casida et al 1993;Methfessel 1992).…”