Calming the Brain : Benzodiazepines and Related Drugs from Laboratory to Clinic

This book covers the entire field of research in the area of minor tranquillizers and its application to current clinical practice in the treatment of anxiety and insomnia. These drugs are principally the benzodiazepines and related drugs with a similar mechanism of action, such as zolpidem and zopiclone. The molecular mechanism of action of benzodiazepines is described, focussing on the interaction of these drugs with the different isoform of the GABAA^O receptor, and the consequences of this for brain function. Recent advances in this knowledge have provided a framework for defining the physiochemical nature of the interaction between such drugs and their receptor protein, and thus pave the way for the design of new anxiolytic and hypnotic drugs. The animal models available for evaluating the potential of such new therapeutic agents in the treatment of anxiety and insomnia are discussed. Furthermore, understanding of the physiological regulation of the GABAA receptor may provide insights into the aetiopathology of these diseases. The clinical use of benzodiazepines and related drugs in the treatment of anxiety, insomnia, epilepsy and as anaesthetics are explored. The advantages and limitations of such treatments are discussed, and the impact of drugs evaluated. A chapter is devoted to the issue of independence, the clinical pertinence of tolerence and dependence, and evaluates treatment options that may minimise the risk of dependence. Cover......Page 1 Title Page......Page 2 Copyright Page......Page 3 Table of Contents......Page 4 Preface......Page 6 1 The story of modern tranquilliser drugs......Page 8 2 Interaction of the benzodiazepines with the GABAA receptor......Page 22 3 Structural characterisation of the GABAA receptor......Page 50 4 Functional characterisation of the GABAA receptor......Page 76 5 Structures of benzodiazepine recognition site ligands......Page 92 6 Behavioural pharmacology......Page 106 7 Pharmacokinetic determinants of clinical activity......Page 138 8 Benzodiazepine drugs in sleep disorders......Page 152 9 Benzodiazepines as anxiolytics......Page 162 10 Benzodiazepines: Anticonvulsant and other clinical uses......Page 174 11 Conclusions......Page 184 Index......Page 188