The structure-function relationship between the alkaloids physostigmine, physovenine and the three structurally related compounds were investigated by employing kinetic studies and molecular modeling. Crystallographic data from the X-ray conformation of the Torpedo californica acetylcholinesterase complex together with the transition state analog inhibitor m-(N,N,N,-Trimethylammonio) trifluoroacetophenone (TMTFA) was used as template onto which inhibitors were superimposed. Among the structural elements of the active site, TRP84 residue shows a versatile role. In fact, its aromatic electrons not only can be employed in pi-cation interactions, as is the case for ACh, but they can also provide a polarizable surface for van der Waals and London interactions.