Literature DB >> 23398473

Selective mGAT2 (BGT-1) GABA uptake inhibitors: design, synthesis, and pharmacological characterization.

Stine B Vogensen1, Lars Jørgensen, Karsten K Madsen, Nrupa Borkar, Petrine Wellendorph, Jonas Skovgaard-Petersen, Arne Schousboe, H Steve White, Povl Krogsgaard-Larsen, Rasmus P Clausen.   

Abstract

β-Amino acids sharing a lipophilic diaromatic side chain were synthesized and characterized pharmacologically on mouse GABA transporter subtypes mGAT1-4. The parent amino acids were also characterized. Compounds 13a, 13b, and 17b displayed more than 6-fold selectivity for mGAT2 over mGAT1. Compound 17b displayed anticonvulsive properties inferring a role of mGAT2 in epileptic disorders. These results provide new neuropharmacological tools and a strategy for designing subtype selective GABA transport inhibitors.

Entities:  

Mesh：

Substances：

Year:  2013        PMID： 23398473     DOI： 10.1021/jm301872x

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  9 in total

1.  Pharmacological identification of a guanidine-containing β-alanine analogue with low micromolar potency and selectivity for the betaine/GABA transporter 1 (BGT1).

Authors:  Anas Al-Khawaja; Jette G Petersen; Maria Damgaard; Mette H Jensen; Stine B Vogensen; Maria E K Lie; Bolette Kragholm; Hans Bräuner-Osborne; Rasmus P Clausen; Bente Frølund; Petrine Wellendorph
Journal:  Neurochem Res       Date:  2014-05-23       Impact factor: 3.996

2.  The subcellular localization of GABA transporters and its implication for seizure management.

Authors:  Karsten K Madsen; Gert H Hansen; E Michael Danielsen; Arne Schousboe
Journal:  Neurochem Res       Date:  2014-12-18       Impact factor: 3.996

Review 3.  The GABA synapse as a target for antiepileptic drugs: a historical overview focused on GABA transporters.

Authors:  Arne Schousboe; Karsten K Madsen; Melissa L Barker-Haliski; H Steve White
Journal:  Neurochem Res       Date:  2014-03-14       Impact factor: 3.996

4.  Conformationally Restricted GABA with Bicyclo[3.1.0]hexane Backbone as the First Highly Selective BGT-1 Inhibitor.

Authors:  Takaaki Kobayashi; Akihiro Suemasa; Arisa Igawa; Soichiro Ide; Hayato Fukuda; Hiroshi Abe; Mitsuhiro Arisawa; Masabumi Minami; Satoshi Shuto
Journal:  ACS Med Chem Lett       Date:  2014-06-16       Impact factor: 4.345

5.  Molecular Determinants and Pharmacological Analysis for a Class of Competitive Non-transported Bicyclic Inhibitors of the Betaine/GABA Transporter BGT1.

Authors:  Stefanie Kickinger; Maria E K Lie; Akihiro Suemasa; Anas Al-Khawaja; Koichi Fujiwara; Mizuki Watanabe; Kristine S Wilhelmsen; Christina B Falk-Petersen; Bente Frølund; Satoshi Shuto; Gerhard F Ecker; Petrine Wellendorph
Journal:  Front Chem       Date:  2021-09-14       Impact factor: 5.545

6.  Astrocytic Control of Biosynthesis and Turnover of the Neurotransmitters Glutamate and GABA.

Authors:  Arne Schousboe; Lasse K Bak; Helle S Waagepetersen
Journal:  Front Endocrinol (Lausanne)       Date:  2013-08-15       Impact factor: 5.555

7.  A binding mode hypothesis of tiagabine confirms liothyronine effect on γ-aminobutyric acid transporter 1 (GAT1).

Authors:  Andreas Jurik; Barbara Zdrazil; Marion Holy; Thomas Stockner; Harald H Sitte; Gerhard F Ecker
Journal:  J Med Chem       Date:  2015-02-26       Impact factor: 8.039

8.  Pharmacological Characterization of a Betaine/GABA Transporter 1 (BGT1) Inhibitor Displaying an Unusual Biphasic Inhibition Profile and Anti-seizure Effects.

Authors:  Maria E K Lie; Stefanie Kickinger; Jonas Skovgaard-Petersen; Gerhard F Ecker; Rasmus P Clausen; Arne Schousboe; H Steve White; Petrine Wellendorph
Journal:  Neurochem Res       Date:  2020-04-04       Impact factor: 4.414

9.  Exploring the molecular determinants for subtype-selectivity of 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid analogs as betaine/GABA transporter 1 (BGT1) substrate-inhibitors.

Authors:  Stefanie Kickinger; Anas Al-Khawaja; Anne Stæhr Haugaard; Maria E K Lie; Francesco Bavo; Rebekka Löffler; Maria Damgaard; Gerhard F Ecker; Bente Frølund; Petrine Wellendorph
Journal:  Sci Rep       Date:  2020-08-03       Impact factor: 4.996
  9 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.