First Photoswitchable Neurotransmitter Transporter Inhibitor: Light-Induced Control of 纬-Aminobutyric Acid Transporter 1 (GAT1) Activity in Mouse Brain

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• 作者：Gabriele Quandt ; Georg H枚fner ; J枚rg Pabel ; Julien Dine ; Matthias Eder ; Klaus T. Wanner
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：August 14, 2014
• 年：2014
• 卷：57
• 期：15
• 页码：6809-6821
• 全文大小：462K
• ISSN：1520-4804

文摘

Inhibition of mGAT1, the most abundant GABA transporter in the brain, enhances GABA signaling and alleviates symptoms of CNS disorders such as epilepsy assumed to be associated with low GABA levels. We have now developed a potent and subtype selective photoswitchable inhibitor of this transporter, which for the first time extends the photoswitch concept for the light-induced control of ligand affinity to active membrane transporters. The new inhibitor exhibited reduced activity upon irradiation with light, as demonstrated in GABA uptake assays and electrophysiological experiments with brain slices, and might be used as a tool compound for deepening the understanding of mGAT1 function in brain.