check this out:


Further studies on the distinctive sleep-wakefulness profiles of antihistamines (astemizole, ketotifen, terfenadine) in dogs
A. Wauquier *, W. A. E. van Den Broeck, F. Awouters, P. A. J. Janssen
Department of Pharmacology, Janssen Pharmaceutica, Beerse, Belgium

*Correspondence to A. Wauquier, Department of Neuropharmacology, Janssen Pharmaceutica, B-2340 Beerse, Belgium

Keywords
sleep-wakefulness patterns ? dogs ? antihistamines ? astemizole ? ketotifen ? terfenadine

Abstract
The 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.