Characterization of structural requirement for substrates recognition and identification of the molecular entity of proton/organic cation antiporter expressed at the human blood-brain barrier

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16453
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Teikyo University
• Principal Investigator: Tega Yuma 帝京大学, 薬学部, 助教 (50809043)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 血液脳関門 / 塩基性薬物 / トランスポーター / Diphenhydramine誘導体 / 構造活性相関

Outline of Final Research Achievements

Recently, it has been suggested the functionally expression of H+/organic cation antiporter that transport basic drugs into the brain at the human blood-brain barrier, and it is expected to be applied to drug development. However, the molecular entity of H+/organic cation antiporter have not been clarified, and there is little information on the substrate recognition. The present study was performed to clarify the structural requirement, which are important for substrate recognition and transport, and to elucidate the molecular entity.
Although the molecular entity is still unclear, the present results clarified the amine structures that are important for the transport by the H+/organic cation antiporter.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

超高齢社会化に伴い、アルツハイマー病をはじめとする中枢神経疾患の罹患者数は増加しているが、それらに対する医薬品の開発成功率は非常に低いのが現状である。その原因の１つに、血液脳関門によって薬物の脳移行が妨げられることが挙げられる。本研究の成果は、トランスポーターを介した脳への薬部送達に新たな可能性を提示するものであり、中枢を標的としたドラッグデザインや精密な薬物動態予測につながることが期待される。また、新たな中枢薬の開発が促進されることで、中枢神経疾患患者のQOL向上につながるものと期待される。