Slow wave sleep-inducing effects of first generation H-1-antagonists

The present study was performed to see if first-generation histamine H-1-an tagonists are useful sedative-hypnotic drugs. Increases in electroencephalo gram (EEG) power spectra of the delta band (0-4 Hz) at the frontal cortex a nd theta band (4-8 Hz) at the hippocampus in rats were used as an indexes o f sleep. The H-1-antagonists used in this study resulted in a decrease in s leep 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 H -1-antagonists and brotizolam. The order of potency of H-1-antagonists for the reduction in sleep latency (from greatest to least) was promethazine>ch lorpheniramine>diphenhydramine and pyrilamine, and that for the increase in sleep duration was chlorpheniramine>promethazine>diphenhydramine and pyril amine, Brotizolam was more potent than these H-1-antagonists, with 14-18-fo ld and 4-14-fold greater effects on sleep latency and duration, respectivel y. These results clearly show that H-1-antagonists are effective in mild to moderate insomnia as sedative-hypnotic drugs.