1-（3-（9H-咔唑-9-基）-1-丙基）-4-（2-甲氧基苯基）-4-哌啶醇，一种新型的小鼠II型γ-氨基丁酸转运体亚型选择性抑制剂。
1-(3-(9H-carbazol-9-yl)-1-propyl)-4-(2-methoxyphenyl)-4-piperidinol, a novel subtype selective inhibitor of the mouse type II GABA-transporter.
作者信息
Thomsen C, Sørensen P O, Egebjerg J
机构信息
Novo Nordisk A/S, Department of Molecular Pharmacology, Måløv, Denmark.
出版信息
Br J Pharmacol. 1997 Mar;120(6):983-5. doi: 10.1038/sj.bjp.0700957.
The selectivity of new derivatives of the gamma-aminobutyric acid (GABA)-uptake inhibitor, tiagabine was characterized at the four cloned mouse GABA transporters (mGAT1 through mGAT4) by measuring [3H]-GABA uptake into stably transfected baby hamster kidney cells. While tiagabine is a highly selective inhibitor of mGAT1 (Ki = 0.11 +/- 0.02 microM), these derivatives exhibited low potencies at mGAT1 but differential activities at mGAT2, mGAT3 and mGAT4. In particular, 1-(3-(9H-carbazol-9-yl)-1-propyl)-4-(2-methoxyphenyl)-4-piperidino l (NNC 05-2090) was a potent inhibitor of mGAT2 (Ki = 1.4 +/- 0.3 microM) showing at least 10 fold selectivity over mGAT1, mGAT3 and mGAT4. NNC 05-2090 is the first subtype selective inhibitor of mGAT2 and may represent a novel useful tool for investigating the physiological roles of GAT2 in the brain and periphery.
通过测量[3H]-γ-氨基丁酸（GABA）摄取到稳定转染的幼仓鼠肾细胞中的情况，对GABA摄取抑制剂替加宾的新衍生物的选择性进行了表征，该表征是针对四种克隆的小鼠GABA转运体（mGAT1至mGAT4）进行的。虽然替加宾是mGAT1的高度选择性抑制剂（Ki = 0.11±0.02 microM），但这些衍生物在mGAT1上表现出低效性，而在mGAT2、mGAT3和mGAT4上具有不同的活性。特别是，1-(3-(9H-咔唑-9-基)-1-丙基)-4-(2-甲氧基苯基)-4-哌啶醇（NNC 05-2090）是mGAT2的有效抑制剂（Ki = 1.4±0.3 microM），对mGAT1、mGAT3和mGAT4的选择性至少高10倍。NNC 05-2090是首个mGAT2亚型选择性抑制剂，可能代表一种用于研究GAT2在脑和外周生理作用的新型有用工具。
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