Effects of second-generation histamine H₁ receptor antagonists on the sleep-wakefulness cycle in rats

The present study was performed to examine the sedative effects of second-generation histamine H₁ receptor antagonist using power spectrum analysis in the rat. Similar to ketotifen, olopatadine caused a decrease in sleep latency at a dose of 50 mg/kg, while epinastine and cetirizine showed no significant effect even at a dose of 50 mg/kg. On the other hand, no significant difference was observed in the total times of wakefulness, non-rapid eye movement sleep and rapid eye movement sleep by any drugs used in the experiments. The number of sleep phases and interval between sleep phases were also unchanged by these drugs. Ketotifen and olopatadine inhibited [ ³H]mepyramine binding to rat brain homogenates in parallel with a decrease in sleep latency. No significant effect was observed with epinastine and cetirizine on [³H]mepyramine binding. These findings suggest that the differences in the central nervous system (CNS) depressant effect observed in second generation H₁ receptor antagonists may be due to their liability to penetrate into the CNS.