Brain penetration of cationic drugs is an important determinant of their efficacy and side effects. However, the effects of alterations in the activity of uptake transporters in the brain under inflammatory conditions on the brain penetration of cationic drugs are not fully understood. The aim of this study was to examine changes in brain penetration of cationic drugs, including diphenhydramine (DPHM), memantine (MMT), and cimetidine (CMD), and changes in the expression of uptake transporters such as organic cation transporter (Oct) in brain microvascular endothelial cells (BMECs) under inflammatory conditions. To clarify the effects of inflammation on the brain penetration of DPHM, MMT, and CMD, we performed brain microdialysis studies in a rat model of adjuvant-induced arthritis (AA). Further, differences in transporter mRNA expression levels between BMECs from control and AA rats were evaluated. Brain microdialysis showed that the unbound brain-to-plasma partition coefficient (K_p,uu,brain) for DPHM and MMT was significantly lower in AA rats compared with control rats. OCT mRNA levels were increased and proton-coupled organic cation (H⁺/OC) antiporter mRNA levels were decreased in AA rats compared with control rats. Taken together, our findings suggest that inflammation decreases the brain penetration of H⁺/OC antiporter substrates such as DPHM and MMT.

阳离子药物的脑渗透是其疗效和副作用的重要决定因素。然而，炎症条件下脑内摄取转运蛋白活性的改变对阳离子药物脑渗透的影响尚不完全清楚。本研究的目的是检查阳离子药物的脑渗透变化，包括苯海拉明 (DPHM)、美金刚 (MMT) 和西咪替丁 (CMD)，以及摄取转运蛋白如有机阳离子转运蛋白 (Oct) 的表达变化。炎症条件下的脑微血管内皮细胞（BMECs）。为了阐明炎症对 DPHM、MMT 和 CMD 脑渗透的影响，我们在佐剂性关节炎 (AA) 大鼠模型中进行了脑微透析研究。进一步，评估了来自对照和 AA 大鼠的 BMECs 之间转运蛋白 mRNA 表达水平的差异。脑微透析显示未结合的脑-血浆分配系数 (与对照大鼠相比，AA 大鼠的 DPHM 和 MMT 的K _{p,uu,brain ) 显着降低。}与对照大鼠相比，AA 大鼠的 OCT mRNA 水平升高，质子偶联有机阳离子 (H ⁺ /OC) 逆向转运蛋白 mRNA 水平降低。总之，我们的研究结果表明炎症降低了 H ⁺ /OC 逆向转运蛋白底物（如 DPHM 和 MMT）的脑渗透。