Slow wave sleep-inducing effects of first generation H1-antagonists.
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.
Saitou
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Kaneko
Y
Y
Sugimoto
Y
Y
Chen
Z
Z
Kamei
C
C
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002744:Chlorpheniramine / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects*
D001381:Azepines; D006634:Histamine H1 Antagonists; D006993:Hypnotics and Sedatives; D002744:Chlorpheniramine; C020960:brotizolam; D004155:Diphenhydramine; D011738:Pyrilamine