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

• Material Type: 博士論文
• Title: Examination of the antiepileptic effects of valacyclovir using kindling mice : search for novel antiepileptic agents by drug repositioning using a large medical information database
• Author/Editor: 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
• Author Heading: 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
• Publication, Distribution, etc.: Elsevier
• Publication Date: 2021-04-25
• Publication Date (W3CDTF): 2021-04-25
• Alternative Title: 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
• Periodical title: European Journal of Pharmacology
• No. or year of volume/issue: 902
• Volume: 902
• Pages: 174099-
• ISSN (Periodical Title): ISSN : 0014-2999
• Degree grantor/type: 徳島大学
• Date Granted: 2021-09-09
• Dissertation Number: 甲第3540号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Epilepsy; Large medical information database; Anticonvulsants; Drug repositioning; Kindling; Valacyclovir
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
• Related Material (DOI): 10.1016/j.ejphar.2021.174099
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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http://repo.lib.tokushima-u.ac.jp/files/public/11/116301/20210929171828942318/k3540_abstract_review.pdf fulltext

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