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ID 116301
タイトル別表記
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
著者
高橋, 志門 徳島大学大学院医科学教育部(医学専攻)
武智, 研志 Matsuyama University
Jozukuri, Natsumi Tokushima University
Niimura, Takahiro Tokushima University
中馬, 真幸 Asahikawa Medical University
今西, 正樹 Tokushima University
堀ノ内, 裕也 Tokushima Bunri University
キーワード
Epilepsy
Large medical information database
Anticonvulsants
Drug repositioning
Kindling
Valacyclovir
資料タイプ
学位論文
抄録
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.
掲載誌名
European Journal of Pharmacology
ISSN
00142999
cat書誌ID
AA00639687
AA11527211
出版者
Elsevier
902
開始ページ
174099
発行日
2021-04-25
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Shimon Takahashiの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3540号
学位記番号
甲医第1507号
学位授与年月日
2021-09-09
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系
薬学系