Five subtypes of muscarinic acetylcholine receptors have been identified in mammalian tissues, but the selectivity of ligands that are active at these receptors is low. It is possible, however, that selective compounds may be developed by targeting their allosteric site(s). Important new insights into the mechanism of allosteric control of muscarinic receptors have been obtained recently in investigations of the allosteric effects of neuromuscular blockers, and competition between ligands for the allosteric binding site has now been demonstrated. It is now apparent that the binding site for most allosteric ligands is close to the binding site for acetylcholine but that it is located at a more extracellular position. Stanislav Tucek and Jan Proska discuss the pharmacological implications of ligand interaction at these two sites and the therapeutic possibilities.

Institute of Physiology Academy of Sciences of the Czech Republic Prague

References provided by Crossref.org

Divergence of allosteric effects of rapacuronium on binding and function of muscarinic receptors

Interactions between allosteric modulators and 4-DAMP and other antagonists at muscarinic receptors: potential significance of the distance between the N and carboxyl C atoms in the molecules of antagonists

Subtype-selective inhibition of [methyl-3H]-N-methylscopolamine binding to muscarinic receptors by alpha-truxillic acid esters

Activation of muscarinic acetylcholine receptors via their allosteric binding sites