2021 Fiscal Year Final Research Report
Elucidation of pharmacotherapeutic roles of xenobiotic uptake membrane transporters in epileptic seizures
| Project/Area Number |
19K07126
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47040:Pharmacology-related
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| Research Institution | Takasaki University of Health and Welfare |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 脳・神経 / 脳神経疾患 / 神経科学 / 薬理学 / 輸送担体 |
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| Outline of Final Research Achievements |
To clarify the pharmacotherapeutic role of the carnitine/organic cation transporter OCTN1 in epileptic seizures, we examined the effects of the deficiency of octn1 gene and the administration of the in vivo substrate of OCTN1, ergothioneine (ERGO), on pentylenetetrazole (PTZ)-induced convulsive seizures in mice. The deficiency of octn1 gene and the oral administration of ERGO suppressed PTZ-induced seizures. A plant alkaloid homostachydrine was identified as an in vivo substrate of OCTN1. The possibility that the xenobiotic uptake transporter OCTN1 may deteriorate PTZ-induced seizures through the transport of homostachydrine was shown.
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| Free Research Field |
神経薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
OCTN1の遺伝子欠損によりマウスに目立ったフェノタイプが現れないことから、OCTN1に特異性の高い阻害剤を開発することにより、副作用の少ないてんかん治療薬の開発につながることが期待される。また、食品由来成分のERGOは副作用の少ない安全な化合物であり、生体内濃度がOCTN1によって制御されることから体内動態が予測しやすく、脳移行性も高い。ERGOをシード化合物とした脳移行性の高い安全かつ体内動態を制御しやすい精神・神経疾患治療薬開発への応用が期待される。
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