Structure-Activity Relations for Neurotransmitter Receptor Agonists and Antagonists

Abstract

Until fairly recently, the only way of discovering anything about the nature of postsynaptic receptors for neurotransmitters was the time-honored method of studying the structure-activity relationships of agonists and antagonists. This information was usually incidental to the main practical preoccupation of finding compounds that were pharmacologically more active and specific. The nature of the information obtainable about receptors by this method is, of course, limited. One may show, for example, that in a particular drug certain chemical groups are essential for activity. Depending on the nature of these groups, it is possible to hypothesize binding via ionic or hydrogen bonds and van der Waals or hydrophobic interactions. However, the nature of the receptor components through which these interactions occur is in most cases totally unknown. There is also the problem that unless one works with conformationally rigid moelcules the actual shape of the drug on interaction with the receptor is uncertain. In recent years, more direct attempts have been made to learn something of the chemical nature of various receptors by actual isolation of the macromolecules thought to comprise the receptor material. An extensive review of earlier work in this area using a variety of reversible and irreversible agonists and antagonists has been published (Ehrenpreis et al., 1969). More recent studies are dealt with elsewhere in this series (Hollenberg and Cuatrecasas, Chap. 5, this volume; Changeux, Chap. 7, Vol. 6; Snyder, Chap. 6, Vol. 5).