Sleep disorders and anxiety: biochemical antecedents and pharmacological consequences

Evidence is presented that the most widely used and effective drugs used in the treatment of anxiety and insomnia act by indirectly activating GABA-A receptors in limbic regions of the brain. Since the discovery of the benzodiazepines, different classes of benzodiazepine receptor ligands (such as the cyclopyrroliones and imidazopyridines) have been developed which alleviate anxiety and insomnia by activating different sites on the benzodiazepine-GABA receptor complex to those activated by the 'classical' benzodiazepines as exemplified by temazepam and diazepam. There is evidence that natural ligands also exist in the mammalian brain which can modulate the benzodiazepine-GABA receptor complex. This raises the possibility that insomnia and anxiety states may arise as a consequence of a deficit in the availability of endogenous ligands that act as agonists at these sites.