Transport aross the blood-brain barrier in relation to CNS actions of opioid analgesics

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08080
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Teikyo University
• Principal Investigator: Okura Takashi 帝京大学, 薬学部, 教授 (80326123)
• Co-Investigator(Kenkyū-buntansha): 樋口 慧 帝京大学, 薬学部, 助教 (10625304) ; 出口 芳春 帝京大学, 薬学部, 教授 (40254255) ; 平田 圭一 帝京大学, 薬学部, 助手 (80424852) ; 中谷 絵理子 帝京大学, 薬学部, 助教 (90803916)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 血液脳関門 / オピオイド鎮痛薬

Outline of Final Research Achievements

We have developed simultaneous estimation method for potential brain transfer of multiple opioid analgesics by combination of brain microdialysis method and cocktail dosing. The oxycodone transporter at the blood-brain barrier generates higher unbound concentration gradient of oxycodone in the brain than in the plasma. The oxycodone transporter stimulates brain transfer and CNS action of this drug. The oxycodone transporter transfers several CNS-acting cationic drugs including memantine. To estimate CNS action of opioid analgesics in brain regions, we have obtained fundamental information for measurement of brain receptor occupancy by using high-performance liquid chromatograph-mass spectrometer and confocal fluorescence microscopy.

Free Research Field

薬物動態学、薬力学