Modern drug discovery programs have, since the mid-1960s, been evolving into active collaborative efforts between pharmacologists, biochemists and medicinal chemists. One of the goals of this book is to illustrate how this modus operandi is applied to contemporary research in the area of antianxiety agents. Chapter 1 deals with what has by now become the most basic tool in the drug discovery process: radioligand displacement studies on the receptor site. The current state of knowledge regarding the nature of the receptor which mediates anxiety is detailed, and strategies for the identification of antianxiety agents which exploit this knowledge are discussed. Chapter 2 summarizes and evaluates the pharmacological methodology currently in use in screening anxiolytic agents and predicting possible profiles in humans. Applications of these techniques to several compounds of current interest are discussed. Another objective of the book is to provide a comprehensive summary of the chemistry and structure-activity work in the area to date. Chapter 3 deals with the large body of work in the benzodiazepine series, with particular emphasis on more recent analogs bearing fused rings.
In chapter 4, the author attempts to summarize the work on nonbenzodiazepine anxiolytics. These are a structurally diverse group of compounds which show very interesting profiles of activity both in vitro and in vivo. A final goal in assembling this book was to provide to those contemplating work in this area a springboard from which a rational, directed and efficient drug discovery program may be launched.