Melatonin and S-20098 increase REM sleep and wake-up propensity without modifying NREM sleep homeostasis

Am J Physiol. 1997 Apr;272(4 Pt 2):R1189-96. doi: 10.1152/ajpregu.1997.272.4.R1189.


The pineal hormone melatonin has been implicated in the circadian regulation of sleep. In a crossover design, we investigated the effect of acute administration of 5 mg melatonin and a melatonin agonist (S-20098, 5 and 100 mg) in healthy young men when given 5 h before bedtime on sleep structure and electroencephalogram (EEG) power density. Each trial comprised a baseline, a treatment, and a posttreatment sleep episode. Relative to the placebo condition, all treatments phase advanced the core body temperature rhythm [Kräuchi, K., C. Cajochen, D. Möri, C. Hetsch, and A. Wirz-Justice. Sleep Res. 24: 526, 1995; and Kräuchi, K., C. Cajochen, D. Möri, and A. Wirz-Justice. Am. J. Physiol. 272 (Regulatory Integrative Comp. Physiol. 41): R1178-1188, 1997]. Rapid eye movement (REM) sleep was increased after both melatonin and S-20098. This increase in REM sleep was most pronounced in the first REM sleep episode. On the posttreatment night after melatonin and S-20098 administration, more wakefulness was present in the latter one-half of the sleep episode. EEG power density between 0.25 and 20 Hz during either non-REM (NREM) or REM sleep did not differ from placebo. Thus a single early evening dose of melatonin or the agonist S-20098 increases REM sleep propensity and advances sleep termination while, at the same time, the EEG in NREM sleep remains unaffected.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / administration & dosage
  • Acetamides / pharmacology*
  • Adult
  • Cross-Over Studies
  • Darkness
  • Double-Blind Method
  • Drug Administration Schedule
  • Homeostasis
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / pharmacology*
  • Light
  • Male
  • Melatonin / administration & dosage
  • Melatonin / agonists
  • Melatonin / pharmacology*
  • Placebos
  • Random Allocation
  • Regression Analysis
  • Sleep Stages / drug effects*
  • Sleep, REM / drug effects*
  • Wakefulness / drug effects*


  • Acetamides
  • Hypnotics and Sedatives
  • Placebos
  • agomelatine
  • Melatonin