M1 muscarinic cetylcholine receptor allosteric modulators as potential therapeutic opportunities for treating Alzheimer's disease

Abstract

In this review the various chemical structures of allosteric agonists and modulators of the muscarinic acetylcholine receptor subtype 1 (mAChR₁ or M₁) and their relevance for possible treatment of Alzheimer's disease (AD) are discussed. Furthermore, their design principles, common structural properties and their unique features with regard to structure–activity relationships (SARs), such as ‘molecular switches’ and ‘steep/flat’ SARs, are highlighted. M₁ bitopic ligands and hybrid molecules are also considered. All these differently designed M₁ allosteric modulators open exciting new paths in medicinal chemistry with most promising therapeutic opportunities to fight AD.