Further studies on the distinctive sleep‐wakefulness profiles of antihistamines (astemizole, ketotifen, terfenadine) in dogs

Abstract

AbstractThe effects of the antihistamines astemizole, ketotifen, and terfenadine, given orally at the dose of 10 mg/kg, were investigated on 16‐hr sleep‐wakefulness patterns in dogs. As determined in the Ascaris allergy test in dogs, this dose had marked antihistaminic activity for at least the total duration of the recording. Using a computerized on‐line analysis and automatic sleep classification, a differentiation was made between wakefulness, transition to sleep, slow‐wave sleep, and REM (or paradoxical) sleep. Astemizole did not significantly change sleep‐wakefulness patterns. Ketotifen significantly increased slow‐wave sleep and significantly decreased REM sleep. Terfenadine significantly decreased wakefulness and significantly increased both slow‐wave sleep and REM sleep. With both ketotifen and terfenadine, REM latency was prolonged. Two different mechanisms appear to be involved in the REM sleep effects seen with terfenadine: an early REM sleep suppressant effect and a late but large REM sleep‐enhancing effect. This study shows central effects of terfenadine that are not completely typical for H1 antagonists but which are very pronounced at a dose producing much weaker peripheral antihistamine activity than the same dose of ketotifen and astemizole.