Electrostatic Potential Surfaces of 5-HT3R Agonists Suggest Accessory Cation–π Site Adjacent to Agonist Binding Domain

Electrostatic potential surface mapping of various aromatic ring systems contained in 5-HT3R agonists indicate that some agonists contain an aromatic moiety capable of a favorable cation–π interaction next to the e-face of pyridine (or its bioisostere). A pharmacophore model has been proposed based on superimposition of two distinct ‘aryl’ interactions.