Shigemoto Yuki, Shinomiya Kazuaki, Mio Mitsunobu, Azuma Nobuhide, Kamei Chiaki
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
Eur J Pharmacol. 2004 Jun 28;494(2-3):161-5. doi: 10.1016/j.ejphar.2004.05.010.
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.
本研究旨在通过功率谱分析检测第二代组胺H(1)受体拮抗剂在大鼠体内的镇静作用。与酮替芬相似，奥洛他定在50mg/kg剂量时可使睡眠潜伏期缩短，而依匹斯汀和西替利嗪即使在50mg/kg剂量时也无显著作用。另一方面，实验中使用的任何药物对清醒总时长、非快速眼动睡眠和快速眼动睡眠的总时长均未观察到显著差异。这些药物对睡眠阶段数量和睡眠阶段间隔也无影响。酮替芬和奥洛他定抑制[(3)H]美吡拉敏与大鼠脑匀浆的结合，同时睡眠潜伏期缩短。依匹斯汀和西替利嗪对[(3)H]美吡拉敏结合无显著影响。这些发现表明，第二代H(1)受体拮抗剂在中枢神经系统（CNS）抑制作用上的差异可能与其穿透CNS的能力有关。
