Scientists have been looking for a natural brain chemical that helps you fall asleep since the 1970s. In rats, a mixture called the sleep‑promoting substance (SPS) – which includes at least four parts, one of them uridine – made the animals less active and increased deep and REM sleep when given at night. The effect changed depending on the time of day, showing that sleep chemicals work with your internal clock.

Time-consuming studies in search of an endogenously occurring sleep substance started early in this century. The historical background of this field of sleep science is briefly reviewed. The search for "sleep-promoting substance (SPS)" started in 1972. A bioassay technique was developed based on the monitoring of the circadian sleep-waking rhythm in freely moving male rats. The partially purified SPS from the brainstem of 24-h sleep-deprived rats caused a reduction in locomotor activity and an increase in both slow wave sleep and paradoxical sleep, when nocturnally administered by either the intraperitoneal or intracerebroventricular route. SPS is composed of at least 4 different effective fractions, including uridine. The sleep-inducing and sleep-maintaining potencies of several putative sleep substances were compared. Circadian variations in their effectiveness were apparent. The role of sleep substances in sleep regulation is discussed.