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ID 116301
Title Alternative
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
Author
Takahashi, Shimon Tokushima University
Takechi, Kenshi Matsuyama University
Jozukuri, Natsumi Tokushima University
Chuma, Masayuki Asahikawa Medical University
Horinouchi, Yuya Tokushima Bunri University
Keywords
Epilepsy
Large medical information database
Anticonvulsants
Drug repositioning
Kindling
Valacyclovir
Content Type
Thesis or Dissertation
Description
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.
Journal Title
European Journal of Pharmacology
ISSN
00142999
NCID
AA00639687
AA11527211
Publisher
Elsevier
Volume
902
Start Page
174099
Published Date
2021-04-25
Remark
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。
Rights
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3540号
Diploma Number
甲医第1507号
Granted Date
2021-09-09
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences
Pharmaceutical Sciences