Examination of the antiepileptic effects of valacyclovir using kindling mice : search for novel antiepileptic agents by drug repositioning using a large medical information database

• 資料種別: 博士論文
• ISSN: 0014-2999
• タイトル: Examination of the antiepileptic effects of valacyclovir using kindling mice : search for novel antiepileptic agents by drug repositioning using a large medical information database
• 巻次・部編番号: 902
• 著者・編者: Takahashi, Shimon; Takechi, Kenshi; Jozukuri, Natsumi; Niimura, Takahiro; Chuma, Masayuki; Goda, Mitsuhiro; Zamami, Yoshito; Izawa-Ishizawa, Yuki; Imanishi, Masaki; Horinouchi, Yuya; Ikeda, Yasumasa; Tsuchiya, Koichiro; Yanagawa, Hiroaki; Ishizawa, Keisuke
• 著者標目: Takahashi, Shimon; Takechi, Kenshi; Jozukuri, Natsumi; Niimura, Takahiro; Chuma, Masayuki; Goda, Mitsuhiro; Zamami, Yoshito; Izawa-Ishizawa, Yuki; Imanishi, Masaki; Horinouchi, Yuya; Ikeda, Yasumasa; Tsuchiya, Koichiro; Yanagawa, Hiroaki; Ishizawa, Keisuke
• 出版事項: Elsevier
• 出版年月日等: 2021-04-25
• 出版年（W3CDTF）: 2021-04-25
• 並列タイトル等: キンドリングマウスを用いたバラシクロビルの抗てんかん作用の検討 : 大規模医療情報データベースを用いたドラッグリポジショニングによる新規抗てんかん薬の探索
• タイトル（掲載誌）: European Journal of Pharmacology
• 授与機関名: 徳島大学
• 授与年月日: 2021-09-09
• 授与年月日（W3CDTF）: 2021-09-09
• 報告番号: 甲第3540号
• 学位: 博士（医学）
• 博論授与番号: 甲第3540号
• 本文の言語コード: eng
• 件名標目: Epilepsy; Large medical information database; Anticonvulsants; Drug repositioning; Kindling; Valacyclovir
• 対象利用者: 一般
• 一般注記: Despite the availability of more than 20 clinical antiepileptic drugs, approximately 30% of patients with epilepsy do not respond to antiepileptic drug treatment. Therefore, it is important to develop antiepileptic products that function via novel mechanisms. In the present study, we evaluated data from one of the largest global databases to identify drugs with antiepileptic effects, and subsequently attempted to understand the effect of the combination of antiepileptic drugs and valacyclovir in epileptic seizures using a kindling model. To induce kindling in mice, pentylenetetrazol at a dose of 40 mg/kg was administered once every 48 h. Valacyclovir was orally administered 30 min before antiepileptic drug injection in kindled mice, and behavioral seizures were monitored for 20 min following pentylenetetrazol administration. Additionally, c-Fos expression in the hippocampal dentate gyrus was measured in kindled mice. Valacyclovir showed inhibitory effects on pentylenetetrazol-induced kindled seizures. In addition, simultaneous use of levetiracetam and valacyclovir caused more potent inhibition of seizure activity, and neither valproic acid nor diazepam augmented the anti-seizure effect in kindled mice. Furthermore, kindled mice showed increased c-Fos levels in the dentate gyrus. The increase in c-Fos expression was significantly inhibited by the simultaneous use of levetiracetam and valacyclovir. The findings of the present study indicate that a combination of levetiracetam and valacyclovir had possible anticonvulsive effects on pentylenetetrazol-induced kindled epileptic seizures. These results suggest that valacyclovir may have an anti-seizure effect in patients with epilepsy.
• DOI: info:doi/10.1016/j.ejphar.2021.174099; https://doi.org/info:doi/10.1016/j.ejphar.2021.174099
• 国立国会図書館永続的識別子: info:ndljp/pid/11864507; https://dl.ndl.go.jp/pid/11864507
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2021-11-08T14:10:24+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://repo.lib.tokushima-u.ac.jp/116301
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp