1. This paper is dedicated to the memory of Sir D. H. R. Barton for the fundamental contributions he made in conformation and its importance in chemistry. It was Barton, at a cocktail party following a research seminar at the University of Wisconsin in the 1950s, who discussed with Edward E. Smissman the thoughts Barton had of the importance of conformation to organic chemistry that sparked Smissman's realization of the relevance of conformation to the interaction of drugs with receptors. Smissman embarked on his highly successful research in the 1950s and 1960s to exploit this with the design and synthesis of conformationally-restricted (rigid) analogues of drugs and neurotransmitters. Today the concept of rigid analogues in drug design is taken for granted, and it was Smissman, later reinforced by conversations this author had with Barton, that sparked my own interest in applications of the concept of rigid analogues to an understanding of the molecular mechanism of action of amphetamine, and further to the subject of this paper. Both men were giants in their field, and it is noteworthy that there was a synergism in the recognition of the work of one by the other in ways that neither would have seen alone.
2. Taken in large part from the Ph.D. dissertation of T.M.C., University of Kansas, 1998.
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