Bisquaternary caracurine V derivatives as allosteric modulators of ligand binding to M2 acetylcholine receptors

Bioorg Med Chem Lett. 2000 Nov 20;10(22):2529-32. doi: 10.1016/s0960-894x(00)00509-6.


The allosteric effect on muscarinic acetylcholine M2 receptors of 11 bisquaternary salts of the Strychnos alkaloid caracurine V was determined. The effect was indicated by the concentration which retarded the rate of dissociation of the antagonist [3H]-N-methylscopolamine from porcine cardiac cholinoceptors by a factor of 2 (EC50). The most potent compounds carry allyl and propargyl substituents, respectively. Introduction of more bulky substituents (e.g., benzyl groups) resulted in a considerably reduced allosteric potency. The wide range of EC50 values (3 nM for R = allyl. 1750 nM for R = 2-naphthyl) suggests a sterically restricted binding pocket. Molecular modeling studies indicated that the caracurine V ring system satisfies the pharmacophore model for the allosteric interaction.

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / pharmacology*
  • Allosteric Regulation
  • Animals
  • Ligands
  • Protein Binding
  • Receptor, Muscarinic M2
  • Receptors, Muscarinic / drug effects*
  • Receptors, Muscarinic / metabolism
  • Swine


  • Alkaloids
  • Ligands
  • Receptor, Muscarinic M2
  • Receptors, Muscarinic
  • caracurine V