[Sleep-modulation and hypnotics: effects of benzodiazepine-receptor's agonists]

As binding sites of the alpha-amino butyric acid receptor complexes benzodiazepine-receptors offer a possibility to enhance hyperpolarization-based inhibition by allosteric modulation. Most of the hypnotic drugs are compounds that bind to benzodiazepine receptors. The effects of these drugs are usually characterized at a descriptive level, without deliberation of the basic processes involved in sleep regulation. This review follows the analysis of hypnotic's effect from a perspective of homeostatic, circadian, ultradian and microstructural regulation of sleep. In contrast to their expected effect benzodiazepines produce a decrease in most of the markers of homeostatic sleep regulation. Ligands with non-benzodiazepine structure (cyclopyrrolones, imidazopyridines, pyrazolopyrimidines) have a permissive or even stimulating effect in some measures of homeostatic sleep regulation. Some benzodiazepines have marked chronobiotic effects, while others interfere with circadian rhythms. The non- benzodiazepine-type hypnotics are mostly free of chronobiotic effects, although zaleplon may increase melatonin release. Given their acute hypothermic effect all hypnotic sedatives mimic the circadian signal of sleep initiation. Ultradian sleep regulation is largely unaffected by hypnotics. The microstructure of sleep as quantified by arousal instability is a sensitive measure of the effect of most of the hypnotics. Hypnotic sedatives decrease arousal instability. Zolpidem has the strongest effects in microstructural terms.