Dosage individualization of antianxiety and sedative medication based on modified synaptic function of cerebral GABAergic neurons with peripheral organs failure

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07220
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Okayama University
• Principal Investigator: Aiba Tetsuya 岡山大学, 医歯薬学域, 准教授 (00231754)
• Co-Investigator(Kenkyū-buntansha): 北村 佳久 就実大学, 薬学部, 教授 (40423339)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 個別化投与 / GABA / 抗不安薬 / TrkB / KCC2

Outline of Final Research Achievements

Susceptibility of the central nerve system toward the sedatives alters with functional impairment of peripheral organ. To clarify and understand mechanism underlying the alteration, we examined altered potentiation of the pharmacological effects of phenobarbital in rats with experimentally induced renal failure. As a result, it was shown that while little alteration was observed regarding the GABA receptor expression, the cerebral expression of chloride transporter protein KCC2 decreases in the rats. An elevated level of the phosphorylated TrkB protein that regulates the KCC2 protein expression was also demonstrated. These findings indicate that the decrease in the KCC protein expression primally accounts for altered susceptibility of the central nerve system, and that the phosphorylation process of the TrkB protein can be considered as the dominant factor for the altered susceptibility.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

薬物療法の個別化至適化は、疾病からの迅速な回復と患者の生活の質のより一層の向上に資するものであり、そしてこうした医療が提供されることで、医療費や社会保障費の抑制・削減、更に省資源化が果たされる。本研究では、特に中枢抑制薬について、その標的組織の薬物感受性の変動機序と変動の決定因子を明らかにした。今回の研究成果に基づき、感受性変動機構の理解が更に深まることで、薬物療法の個別化至適化の高度化が進み、これまで以上に迅速な疾病回復と患者生活の質の向上が図られることが強く期待される。