The effects of four reference antihistamines: ketotifen, diphenhydramine, chlorpheniramine and pyrilamine and of astemizole, a new potent and long-acting antihistamine, were studied on 16 hr sleep-wakefulness patterns in the same dogs. Using a computer-based on-line analysis and automatic stage classification, a differentiation was made between wakefulness, transition to sleep (drowsiness), slow wave sleep and rapid eye movement (REM) sleep. The reference antihistamines significantly increased non-REM sleep. The reference antihistamines significantly increased non-REM sleep: diphenhydramine and chlorpheniramine increased drowsiness, ketotifen increased slow-wave sleep and pyrilamine increased both. All, but astemizole, significantly prolonged the latency to the first REM period, prolonged the interval between successive REM periods and suppressed the total amount of REM sleep. With all antihistamines, the effects were most pronounced for the first 4 hr and there was no within-night rebound. Chlorpheniramine had long-lasting effects throughout the night, especially on REM sleep. The effects on non-REM sleep might be due to a blockage of brain histamine H1receptors, whereas the effects on REM sleep might be due to the anticholinergic properties of the antihistamines. Astemizole was devoid of any significant effect on the sleep-wakefulness pattern, in spite of its long-lasting antihistamine effects, suggesting that the common clinical side-effects of antihistamines, such as sedation and dryness of mucosal surfaces, will be lacking. © 1981.
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