Effects of First- and Second-Generation Histamine-H_1-Receptor Antagonists on the Pentobarbital-Induced Loss of the Righting Reflex in Streptozotocin-Induced Diabetic Mice
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概要
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The second-generation histamine-H1-receptor antagonists, such as epinastine and cetirizine, are used as non-sedating antihistamines for treating allergic symptoms due to their poor ability to penetrate blood-brain barrier. Because it has been reported that the blood-brain barrier system is disturbed in diabetes, it is possible that second-generation histamine-H1-receptor antagonists may easily penetrate the blood-brain barrier and cause potent sedation in diabetics. In the present study, we investigated the effects of first-generation (diphenhydramine) and second-generation (epinastine and cetirizine) histamine-H1-receptor antagonists on the duration of pentobarbital-induced loss of the righting reflex (LORR) in non-diabetic and diabetic mice. Systemic treatment with diphenhydramine (3 – 30 mg/kg, s.c.), and intracerebroventricular treatment with epinastine (0.03 – 0.3 μg/mouse) and cetirizine (0.03 – 0.3 μg/mouse) dose-dependently and significantly increased the duration of pentobarbital-induced LORR in both non-diabetic and diabetic mice. Although systemic treatment with epinastine (3 – 30 mg/kg, s.c.) and cetirizine (3 – 30 mg/kg, s.c.) did not affect the duration of pentobarbital-induced LORR in non-diabetic mice, these treatments significantly prolonged it in diabetic mice. Our results suggest that the systemic administration of second-generation histamine-H1-receptor antagonists may produce a central nervous system depressant effect in diabetes.
- 社団法人 日本薬理学会の論文
- 2005-02-20
著者
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SAITOH Akiyoshi
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hosh
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ONODERA Kenji
Department of Pharmacology, Tohoku University School of Dentistry
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KAMEI Junzo
Department of Pathophysiology, School of Pharmacy and Pharmaceutical Sciences, Hoshi University
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Saitoh Akiyoshi
Department Of Pathophysiology & Therapeutics School Of Pharmacy And Pharmaceutical Sciences Hosh
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MIYATA Shigeo
Department of Pathophysiology & Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi
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HIRANO Shoko
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hosh
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Onodera Kenji
Department Of Dental Pharmacology
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Hirano Shoko
Department Of Pathophysiology And Therapeutics School Of Pharmacy And Pharmaceutical Sciences Hoshi
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Kamei J
Department Of Pathophysiology And Therapeutics Faculty Of Pharmaceutical Sciences Hoshi University
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Kamei Junzo
国立精神･神経センター精神保健研究所 老人精神保健部
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Kamei Junzo
Department Of Pathophysilology & Therapeutics Faculty Of Pharmaceutical Sciences Hoshi Universit
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Miyata Shigeo
Department Of Pathophysiology And Therapeutics School Of Pharmacy And Pharmaceutical Sciences Hoshi
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Saitoh A
Department Of Pathophysiology And Therapeutics School Of Pharmacy And Pharmaceutical Sciences Hoshi
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ONODERA Kenji
Department of Chemical Pharmacology, Tohoku College of Pharmacy
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Saitoh Akiyoshi
Department of Neuropsychopharmacology, National Institute of Mental Health National Center of Neurology and Psychiatry, Japan
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SAITOH Akiyoshi
Department of Neuropsychopharmacology, National Institute of Mental Health National Center of Neurology and Psychiatry
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