Neuropharmacology of sleep induction by benzodiazepines.

Although benzodiazepines (BZs) have been the most widely used sedative/hypnotics for many years, the mechanism by which they induce sleep and the neuroanatomic site(s) at which they act have remained poorly understood. Recent characterization of the central BZ-GABAA receptor complex using molecular biological techniques and sleep studies employing new ligands have begun to elucidate these issues. Although alterations in GABAergic activity are involved in the anticonvulsant and myorelaxant properties of BZs, the significance of GABA function in their hypnotic effects is less clear. The pharmacologic significance of receptor subtypes also remains uncertain. A growing body of evidence indicates that the hypnotic effects of BZs involve alterations in potential-dependent calcium ion flux. In terms of neuroanatomy, BZ effects on sleep may result from actions in the anterior hypothalamus as well as brainstem structures including the dorsal raphe nuclei.