Studies on the Novel Antiallergic Agent HSR-609: Its Penetration into the Central Nervous System in Mice and Guinea Pigs and Its Selectivity for the Histamine H1-Receptor.
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- Kakiuchi Masato
- Research and Development Division, Hokuriku Seiyaku Co., Ltd.
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- Ohashi Tetsuo
- Research and Development Division, Hokuriku Seiyaku Co., Ltd.
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- Musoh Keiichi
- Research and Development Division, Hokuriku Seiyaku Co., Ltd.
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- Kawamura Kimio
- Research and Development Division, Hokuriku Seiyaku Co., Ltd.
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- Morikawa Kouji
- Research and Development Division, Hokuriku Seiyaku Co., Ltd.
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- Kato Hideo
- Research and Development Division, Hokuriku Seiyaku Co., Ltd.
書誌事項
- タイトル別名
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- Studies on the Novel Antiallergic Agent
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We studied the pharmacological characteristics of HSR-609 (3-[4-(8-fluoro-5, 11-dihydrobenz[b]oxepino[4, 3-b]pyridin-11-ylidene)-piperidino]propionic acid dihydrate), a novel amphoteric antiallergic agent, on the central nervous system (CNS). Its selectivity for the histamine H1-receptor and its ability to penetrate into the CNS were compared with those of typical antiallergic agents and the nonamphoteric basic compound PY-608 (8-fluoro-5, 11-dihydro-11-(1-methyl-4-piperidylidene)benz[b]oxepino[4, 3-b]pyridine), which has a chemical structure similar to that of HSR-609. In the in vitro study, HSR-609 had a high affinity for H1-receptors in the guinea pig cerebral cortex in comparison to affinities for muscarinic and serotonin 5-HT2-receptors in the rat cerebral cortex, while the selectivity of PY-608 for the H1receptor was low. The inhibitory effects of these antiallergic agents on histamine-induced increase of vascular permeability in mice (ED50)were compared with the displacement of [3H]mepyramine binding to H1receptors in mouse brain ex vivo (ID50). The ID50/ED50 ratio of HSR-609 was much larger than those of cyproheptadine, ketotifen and PY-608 and larger than those of terfenadine and cetirizine. HSR-609 was found to display selective displacement of the [3H]mepyramine binding to H1-receptors for lung vs cerebral cortex as found with terfenadine in guinea pigs ex vivo. These findings suggest that HSR-609 has high selectivity for the H1-receptor and poor ability to penetrate into the CNS in mice and guinea pigs due to its amphoteric chemical structure.
収録刊行物
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- Jpn.J.Pharmacol.
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Jpn.J.Pharmacol. 73 (4), 291-298, 1997
公益社団法人 日本薬理学会
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詳細情報
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- CRID
- 1390001204287048704
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- NII論文ID
- 10008677708
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- NII書誌ID
- AA00691188
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- COI
- 1:CAS:528:DyaK2sXivVeisL8%3D
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- ISSN
- 13473506
- 00215198
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- NDL書誌ID
- 4196925
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- PubMed
- 9165365
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可