Neuropharmacologic Studies on the Brain Serotonin[1A] Receptor Using the Selective Agonist Osemozotan
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- Matsuda Toshio
- Laboratory of Medicinal Pharmacology, Osaka University Graduate School of Pharmaceutical Sciences Kanazawa University, Hamamatsu University School of Medicine, Chiba University, University of Fukui, Osaka Univeristy United Graduate School of Child Development
書誌事項
- タイトル別名
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- Neuropharmacologic Studies on the Brain Serotonin<sub>1A</sub> Receptor Using the Selective Agonist Osemozotan
- Neuropharmacological studies on brain 5–HT1A receptor using the selective agonist osemozotan
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説明
Alterations in serotonin (5-HT) neurochemistry have been implicated in the etiology of major neuropsychiatric disorders such as anxiety-spectrum disorders, depression, and schizophrenia. The neuromodulatory effects of 5-HT are mediated through 14 receptor subtypes, and those receptors, including the 5-HT1A receptor, are considered to be potential targets for the treatment of psychiatric disorders. We developed the novel 5-HT1A receptor agonist MKC-242 (called osemozotan) and characterized its neurochemical and pharmacological profiles. 5-HT1A receptor agonists modulate the release of amine neurotransmitters through the activation of presynaptic or postsynaptic 5-HT1A receptors in the brain. The agonist has antianxiety and antidepressant effects and improves abnormal behaviors such as aggressive behavior and deficits of prepulse inhibition in isolation-reared mice. We also demonstrated that spinal 5-HT1A receptor activation is involved in isolation rearing-induced hypoalgesia. Concerning the mechanism for induction of isolation-induced abnormal behaviors, we have recently found that the raphe-prefrontal 5-HT system plays a key role in encounter stimulation-induced hyperactivity in isolation-reared mice. Furthermore, we showed that osemozotan attenuates psychostimulant-induced behavioral sensitization and that prefrontal dopamine release is enhanced by functional interaction between the 5-HT1A receptor and other receptors. This review summarizes the neuropharmacology of the 5-HT1A receptor, focusing on our studies using osemozotan, and suggests that the 5-HT1A receptor may be a target molecule for the treatment of psychiatric disorders, pain, and drug dependence.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 36 (12), 1871-1882, 2013
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204633988992
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- NII論文ID
- 130003382066
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC2c3itl2jtw%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 025047268
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- PubMed
- 24292048
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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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- 抄録ライセンスフラグ
- 使用不可