Anxiolytics, 2000 Milestones in Drug Therapy Series

For over thirty years the benzodiazepines monopolised not only the anxiolytic market but also clinical and animal research in anxiety. Indeed many animal tests developed since the 1960s have been optimised for the benzodiazepines and some programmes have even screened candidates as potential anxiolytics on their benzodiazepine-like side-effects rather than their anxiolytic activity. With the realisation of the drawbacks of the benzodiazepines, namely their potential for tolerance and dependency, there has been a renewed interest in alternative anxiolytics both from existing drugs such as the tricyclic and monoamine oxidase antidepressants and from newer agents such as buspirone. In addition anxiety is no longer considered to be a unique entity but rather an umbrella term for a series of specific anxiety disorders such as panic disorder without or with agoraphobia, generalised anxiety disorder (GAD), specific phobias, social phobias and post-traumatic stress disorder (PTSD). These new clinical categories have opened another dimension in the therapy of anxiety requiring the optimisation of treatments for different syndromes. This book is a critical review of today's anxiolytics and those that may become the anxiolytics of tomorrow. What is clear is that currently there are few clinically satisfactory alternatives to the benzodiazepines for the treatment of acute anxiety. For chronic anxiety, it is generally agreed that benzodi­ azepines are not the treatment of first choice. The tricyclic and monoamine oxidase antidepressants, the serotonin reuptake inhibitors and buspirone offer better solutions for chronic anxiety but they are still far from being ideal.

The benzodiazepines: a brief review of pharmacology and therapeutics.- Buspirone.- Tricyclic antidepressants.- Monoamine oxidase inhibitors (including the newer reversible compounds).- Selective serotonin re-uptake inhibitors in anxiety disorders: room for improvement.- Subtype-selective benzodiazepine receptor ligands.- The 5-HT1A receptor: an unkept promise?.- 5-HTIB1 receptors in anxiety.- Brain 5-HT2C receptors: potential role in anxiety disorders.- Glutamate receptor ligands.- Peptide receptors as targets for anxiolytic drugs.