title: Effects of second-generation histamine H1 receptor antagonists on the sleep-wakefulness cycle in rats.
abstract: The present study was performed to examine the sedative effects of second-generation histamine H(1) 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 [(3)H]mepyramine binding to rat brain homogenates in parallel with a decrease in sleep latency. No significant effect was observed with epinastine and cetirizine on [(3)H]mepyramine binding. These findings suggest that the differences in the central nervous system (CNS) depressant effect observed in second generation H(1) receptor antagonists may be due to their liability to penetrate into the CNS.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Shigemoto
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shinomiya
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Mio
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Azuma
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kamei
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011738:Pyrilamine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D006634:Histamine H1 Antagonists; D011738:Pyrilamine