Binding of a ligand to the allosteric pocket of the M1-mAChR can have three effects. (A) A conformational change in the receptor, leading to a change in the binding affinity of the orthosteric-bound ligand, in this case, ACh for the receptor. (B) A broader conformational change, leading to a change (increase or decrease) in the potency of ACh toward a particular signalling response. (C) A direct agonist effect exerted by the allosteric ligand independent of the presence of the orthosteric-bound ligand, ACh.