期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 52, 期 10, 页码 3348-3353出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm8015409
关键词
-
资金
- National Technology Agency of Finland (TEKES)
- Graduate School in Pharmaceutical Research
- Finnish Parkinson Foundation
- Finnish Cultural Foundation
- North Savo Regional fund
- Academy of Finland [108569, 214334, 114721]
- Academy of Finland (AKA) [108569, 214334, 214334, 114721, 108569, 114721] Funding Source: Academy of Finland (AKA)
The brain uptake of solutes is efficiently governed by the blood-brain barrier (BBB). The BBB expresses a number of carrier-mediated transport mechanisms, and new knowledge of these BBB transporters can be used in the rational targeted delivery of drug molecules for active transport. One attractive approach is to conjugate an endogenous transporter substrate to the active drug molecule to utilize the prodrug approach. In the present study, ketoprofen and indomethacin were conjugated with glucose and the brain uptake mechanism of the prodrugs was determined with the in situ rat brain perfusion technique. Two of the prodrugs were able to significantly inhibit the uptake of glucose transporter (GluT1)-mediated uptake of glucose, thereby demonstrating affinity to the transporter. Furthermore, the prodrugs were able to cross the BBB in a temperature-dependent manner, suggesting that the brain uptake of the prodrugs is carrier-mediated.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据