Effects of First- and Second-Generation Histamine-H1-Receptor Antagonists on the Pentobarbital-Induced Loss of the Righting Reflex in Streptozotocin-Induced Diabetic Mice
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- Kamei Junzo
- Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University
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- Hirano Shoko
- Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University
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- Miyata Shigeo
- Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University
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- Saitoh Akiyoshi
- Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University
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- Onodera Kenji
- Department of Dental Pharmacology, Okayama University Graduate School of Medicine and Dentistry
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Abstract
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.<br>
Journal
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 97 (2), 266-272, 2005
The Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390282680152356096
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- NII Article ID
- 10025726218
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- NII Book ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL BIB ID
- 7258513
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- PubMed
- 15699576
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed