Anxiety disorders are common psychiatric problems and the cause of considerable morbidity. Following the demise of the barbiturates, the mainstay of drug treatment for these disorders has been the benzodiazepines. These agents are very effective at producing anxiolysis. However, the disadvantages of their use, including sedation, ataxia and memory impairment, have caused considerable concern to health professionals and the public alike. The other main disadvantage of benzodiazepines is the development of tolerance with continuing use, and subsequent withdrawal symptoms on treatment cessation. In recent years, knowledge of benzodiazepine receptors has increased, and with it the hope that some of the above problems can be addressed by using non-benzodiazepine ligands, subtype specific ligands or partial agonists. The latter bind to benzodiazepine receptor but have lower maximal effects than full agonists, such as diazepam. Thus, they are less efficacious than full agonists and cannot fully potentiate the inhibitory effect of gamma-aminobutyric acid (GABA), even at full receptor occupancy. Animal studies suggest that partial agonists have less propensity to cause adverse effects, although they still retain anxiolytic properties. Importantly, they do not appear to cause significant tolerance and dependence. Several compounds are being developed and, although experience with them is limited, early clinical results appear promising.
