Flavonoids with M1 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 mu M), comparable to that of acetylcholine (K-i = 59 mu M). 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.