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タイトル: | Striatal TRPV1 activation by acetaminophen ameliorates dopamine D2 receptor antagonists-induced orofacial dyskinesia |
著者: | Nagaoka, Koki Nagashima, Takuya Asaoka, Nozomi Yamamoto, Hiroki Toda, Chihiro Kayanuma, Gen Siswanto, Soni Funahashi, Yasuhiro Kuroda, Keisuke Kaibuchi, Kozo Mori, Yasuo Nagayasu, Kazuki https://orcid.org/0000-0002-7438-732X (unconfirmed) Shirakawa, Hisashi https://orcid.org/0000-0002-4129-0978 (unconfirmed) Kaneko, Shuji https://orcid.org/0000-0001-5152-5809 (unconfirmed) |
著者名の別形: | 長岡, 巧樹 長島, 卓也 浅岡, 希美 山本, 浩貴 戸田, 千尋 栢沼, 玄 ソニ, シスワント 船橋, 靖広 黒田, 啓介 貝淵, 弘三 森, 泰生 永安, 一樹 白川, 久志 金子, 周司 |
発行日: | May-2021 |
出版者: | American Society for Clinical Investigation |
誌名: | JCI Insight |
巻: | 6 |
号: | 10 |
論文番号: | e145632 |
抄録: | Antipsychotics often cause tardive dyskinesia, an adverse symptom of involuntary hyperkinetic movements. Analysis of the U.S. Food and Drug Administration Adverse Event Reporting System and JMDC insurance claims revealed that acetaminophen prevents the dyskinesia induced by dopamine D₂ receptor antagonists. In vivo experiments further showed that a 21-day treatment with haloperidol increased the number of vacuous chewing movements (VCMs) in rats, an effect that was inhibited by oral acetaminophen treatment or intracerebroventricular injection of N-(4-hydroxyphenyl)-arachidonylamide (AM404), an acetaminophen metabolite that acts as an activator of the transient receptor potential vanilloid 1 (TRPV1). In mice, haloperidol-induced VCMs were also mitigated by treatment with AM404 applied to the dorsal striatum, but not in TRPV1-deficient mice. Acetaminophen prevented the haloperidol-induced decrease in the number of c-Fos⁺/preproenkephalin⁺ striatal neurons in wild-type mice but not in TRPV1-deficient mice. Finally, chemogenetic stimulation of indirect-pathway medium spiny neurons in the dorsal striatum decreased haloperidol-induced VCMs. These results suggest that acetaminophen activates the indirect pathway neurons by activating TRPV1 channels via AM404. |
記述: | ジスキネジア新治療法の発見 --副作用を減らす併用薬から新しい創薬標的へ--. 京都大学プレスリリース. 2021-04-16. |
著作権等: | © 2021, Nagaoka et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. |
URI: | http://hdl.handle.net/2433/262976 |
DOI(出版社版): | 10.1172/jci.insight.145632 |
PubMed ID: | 33857021 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2021-04-16-2 |
出現コレクション: | 学術雑誌掲載論文等 |
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