Endogenous sleep-substances and sleep regulation.

In the search for endogenous sleep substances two approaches can be distinguished. The homeostatic approach assumes that the sleep substance accumulates during waking and dissipates during sleep. Sleep deprivation has been the principal tool for enhancing the level of a sleep substance in a donor animal before testing its hypnogenic effect in a recipient animal. Among the two sleep factors isolated by this approach, Factor S has been identified as a muramyl peptide, whereas the composition of Sleep Promoting Substance (SPS) has not yet been fully clarified. Recently, factors have been obtained from REM sleep deprived donors which are able to antagonize drug-induced REM sleep suppression in recipients. The homeostatic approach can be related to physiological processes underlying sleep homeostasis and circadian rhythms. The non-homeostatic approach to sleep substances is based on the serendipitous discovery of a hypnogenic action. While a number of such substances have been described, their relationship to physiological sleep regulation is unknown. Melatonin has been reported to induce or enhance sleep in animals and man. However, the doses used in human studies raise the plasma level far beyond the physiological range. Melatonin may influence circadian processes regulating sleep propensity.