Selective allosteric enhancement of the binding and actions of acetylcholine at muscarinic receptor subtypes

摘要: The ternary allosteric model predicts the possibility of discovering molecules with novel and highly subtype-selective modes action. This approach has been applied to muscarinic receptors. alkaloid brucine is capable selectively enhancing by an mechanism effects low but not high concentrations acetylcholine at only m1 subtype A simple derivative brucine, N-chloromethylbrucine, enhances actions m3 In addition it binds to, does affect, properties m4 receptors, thereby demonstrating neutral cooperativity 'absolute' selectivity action receptors over Brucine N-oxide binding m5 These findings allow developing agents that have a targeted mode action; they may act on single receptor which functioning sub-optimally therefore be use therapeutically in early stages Alzheimer's Disease.