Insect muscarinic acetylcholine receptor: pharmacological and toxicological profiles of antagonists and agonists

J Agric Food Chem. 2007 Mar 21;55(6):2276-81. doi: 10.1021/jf0631934. Epub 2007 Feb 24.


The insect muscarinic acetylcholine receptor (mAChR) is evaluated as a potential target for insecticide action. The mammalian M2/M4-selective antagonist radioligand [3H]AF-DX 384 (a pirenzepine analogue) binds to Drosophila mAChR at a single high-affinity site identical to that for the nonselective antagonist [3H]quinuclidinyl benzilate (QNB) and with a pharmacological profile distinct from that of all mammalian mAChR subtypes. Three nonselective antagonists (QNB, scopolamine, and atropine) show the highest affinity (Ki=0.5-2.4 nM) at the Drosophila target, and AF-DX 384 and M3-selective 4-DAMP (dimethyl-4-(diphenylacetoxy)piperidinium iodide) rank next in potency (Ki=5-18 nM). Eleven muscarinic antagonists generally exhibit higher affinity than eight agonists. On injection into houseflies, the antagonists 4-DAMP and (S)-(+)-dimethindene produce suppressed movement, the agonist (methyloxadiazolyl)quinuclidine causes knockdown and tremors, and all of them inhibit [3H]QNB binding ex vivo, indicating possible mAChR-mediated intoxication. The insect mAChR warrants continuing study in lead generation to discover novel insecticides.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / metabolism
  • Drosophila / metabolism
  • Houseflies / metabolism
  • Insecta / metabolism*
  • Muscarinic Agonists / pharmacology*
  • Muscarinic Agonists / toxicity
  • Muscarinic Antagonists / pharmacology*
  • Muscarinic Antagonists / toxicity
  • Pirenzepine / analogs & derivatives
  • Pirenzepine / metabolism
  • Quinuclidinyl Benzilate / metabolism
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / metabolism*
  • Tritium


  • Muscarinic Agonists
  • Muscarinic Antagonists
  • Receptors, Muscarinic
  • Tritium
  • AFDX 384
  • Pirenzepine
  • Quinuclidinyl Benzilate