Andreas Jurik

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Nerve functions require phosphatidylinositol-4,5-bisphosphate (PIP2) that binds to ion channels, thereby controlling their gating. Channel properties are also attributed to serotonin transporters (SERTs); however, SERT regulation by PIP2 has not been reported. SERTs control neurotransmission by removing serotonin from the extracellular space. An increase in(More)
Since the norepinephrine transporter (NET) is involved in a variety of diseases, the investigation of underlying dysregulation-mechanisms of the norepinephrine (NE) system is of major interest. Based on the previously described highly potent and selective NET ligand 1-(3-(methylamino)-1-phenylpropyl)-3-phenyl-1,3-dihydro-2H-benzimidaz- ol-2-one (Me@APPI),(More)
Tiagabine (Gabitril ®) is a selective inhibitor of the human gamma-aminobutyric acid (GABA) transporter 1 (hGAT-1), a transport protein belonging to the family of neurotransmitter-sodium-symporters (NSS). It is a marketed drug, used for treatment of epilepsy. However, the molecular basis of protein-ligand interaction remains obscure due to the lack of a 3D(More)
Background Neuronal functions, such as excitability or endo-and exo-cytosis, require phosphatidylinositol-4,5-bisphosphate (PIP 2) since ion channels and other proteins involved in these processes are regulated by PIP 2. Monoamine transporters control neurotransmission by removing monoa-mines from the extracellular space. They also display channel(More)
Screening a library of small-molecule compounds using a cell line expressing human GABA transporter 3 (hGAT3) in a [(3)H]GABA uptake assay identified isatin derivatives as a new class of hGAT3 inhibitors. A subsequent structure-activity relationship (SAR) study led to the identification of hGAT3-selective inhibitors (i.e., compounds 20 and 34) that were(More)
Elevating GABA levels in the synaptic cleft by inhibiting its reuptake carrier GAT1 is an established approach for the treatment of CNS disorders like epilepsy. With the increasing availability of crystal structures of transmembrane transporters, structure-based approaches to elucidate the molecular basis of ligand-transporter interaction also become(More)
Since high MAO-B levels are present in early stages of AD, the MAO-B system can be designated as an appropriate and prospective tracer target of molecular imaging biomarkers for the detection of early AD. According to the preceding investigations of Mishra et al. the aim of this work was the development of a compound library of selective and reversible(More)
Termination of GABA-ergic signaling requires fast uptake of the neurotransmitter by highly selective transporter proteins. Four subtypes of sodium-and chloride-dependent GABA transporters exist, GAT-1 being the most prominent one in the brain. The only marketed drug targeting this transporter system is the anticonvulsant tiagabine. [1] It is highly GAT-1(More)
The human transporters for the inhibitory neurotrans-mitter gamma-aminobutyric acid (GABA) hGAT-1, 2, and 3, and hBGT-1 belong to the neurotransmitter-sodium symporter (NSS) family of membrane transport proteins. hGAT-1 has been a target for the design of antiepileptic therapeutics [1], with tiagabine (Gabitril ®) being the only GAT inhibitor on the market.(More)
A series of β-amino acids with lipophilic diaromatic side chain was synthesized and characterized pharmacologically on mouse γ-amino butyric acid (GABA) transporter subtypes mGAT1-4 in order to investigate structure activity relationships (SAR) for mGAT2 (corresponding to hBGT-1). Variation in the lipophilic diaromatic side chain was probed to understand(More)
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