Slow wave sleep-inducing effects of first generation H1-antagonists

Biol Pharm Bull. 1999 Oct;22(10):1079-82. doi: 10.1248/bpb.22.1079.


The present study was performed to see if first-generation histamine H1-antagonists are useful sedative-hypnotic drugs. Increases in electroencephalogram (EEG) power spectra of the delta band (0-4 Hz) at the frontal cortex and theta band (4-8 Hz) at the hippocampus in rats were used as an indexes of sleep. The H1-antagonists used in this study resulted in a decrease in sleep latency and an increase in sleep duration (slow wave sleep). The rate of REM (rapid eye movement) sleep during slow wave sleep was decreased by H1-antagonists and brotizolam. The order of potency of H1-antagonists for the reduction in sleep latency (from greatest to least) was promethazine>chlorpheniramine>diphenhydramine and pyrilamine, and that for the increase in sleep duration was chlorpheniramine>promethazine>diphenhydramine and pyrilamine. Brotizolam was more potent than these H1-antagonists, with 14-18-fold and 4-14-fold greater effects on sleep latency and duration, respectively. These results clearly show that H1-antagonists are effective in mild to moderate insomnia as sedative-hypnotic drugs.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Azepines / pharmacology
  • Chlorpheniramine / pharmacology
  • Diphenhydramine / pharmacology
  • Electroencephalography / drug effects
  • Histamine H1 Antagonists / pharmacology*
  • Hypnotics and Sedatives / pharmacology
  • Male
  • Pyrilamine / pharmacology
  • Rats
  • Rats, Wistar
  • Sleep / drug effects*


  • Azepines
  • Histamine H1 Antagonists
  • Hypnotics and Sedatives
  • Chlorpheniramine
  • brotizolam
  • Diphenhydramine
  • Pyrilamine