Flavonoids with M(1) Muscarinic Acetylcholine Receptor Binding Activity

Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer’s disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M(1) muscarinic receptors. Several compounds were found to possess competitive binding affinity (K(i) = 40–110 µM), comparable to that of acetylcholine (K(i) = 59 µM). Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.