Neuromuscular Blocking Properties of Stereoisomeric Androstane‐3, 17‐bisquaternary Ammonium Salts

Many attempts have been made to deduce the configuration of a receptor from studies of the structure and activity of agonist or antagonist drugs. One of the most active fields in this respect has been that of the curare-like agents, and several theories have been advanced to explain the structure-activity relationships of these compounds. The potent neuromuscular blocking activity or ganglion blocking activity of many bisquater- nary ammonium salts has been envisaged in terms of a two-point attachment of the cationic heads to separate anionic receptor sites on the post-synaptic membrane (Barlow & Ing, 1948a, b; Paton & Zaimis, 1948, 1949; Gill, 1959). Deductions about the spatial separation of these receptor sites have been made from a study of the interonium distances of the polymethylene bisquaternary ammonium salts (Barlow, 1960). In this series, peak neuromuscular blocking activity has usually been observed where the maximum possible interonium separation (fully opposed conformation) is ca 14A. How- ever, the use of freely flexible molecules in these studies could be misleading, as has been pointed out by Alauddin & Martin-Smith (1962).