Cholinesterase Inhibitors: Structure of Eserine

ESERINE (physostigmine) was first isolated from the Calabar bean in the latter half of the last century 1 , but it was not until much later that its activity on the heart was demonstrated to be due to inhibition of acetylcholinesterase 2,3 . It is one of the few compounds that are equally active as inhibitors of both true and pseudo-cholinesterase and has been used by many workers as a reference standard in the evaluation of new cholinesterase inhibitors. The chemical structure of this alkaloid was elucidated by Stedman 4 and the absolute configuration has relatively recently been confirmed by use of the nuclear Overhauser effect (NOE) in NMR spectroscopy 5 . As part of our study of the geometry of molecules affecting cholinergic nervous transmission, we have determined the crystal structure.