Abstract
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.
MeSH terms
-
Animals
-
Azo Compounds / chemical synthesis
-
Azo Compounds / chemistry*
-
Azo Compounds / pharmacology
-
Brain / drug effects*
-
Brain / metabolism
-
Brain / radiation effects*
-
GABA Plasma Membrane Transport Proteins / metabolism*
-
GABA Uptake Inhibitors / chemical synthesis
-
GABA Uptake Inhibitors / chemistry*
-
GABA Uptake Inhibitors / pharmacology
-
HEK293 Cells
-
Humans
-
Light
-
Male
-
Mice, Inbred C57BL
-
Nipecotic Acids / chemical synthesis
-
Nipecotic Acids / chemistry*
-
Nipecotic Acids / pharmacology
-
Stereoisomerism
-
Structure-Activity Relationship
Substances
-
1-(2-(2-(3-(2-(naphthalen-1-yl)diazen-1-yl)phenyl)ethoxy)ethyl)piperidine-3-carboxylic acid
-
Azo Compounds
-
GABA Plasma Membrane Transport Proteins
-
GABA Uptake Inhibitors
-
Nipecotic Acids