title: Selective mGAT2 (BGT-1) GABA uptake inhibitors: design, synthesis, and pharmacological characterization.
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.
authors: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
authors: Stine B
authors: SB
authors: Vogensen
authors: Lars
authors: L
authors: Jørgensen
authors: Karsten K
authors: KK
authors: Madsen
authors: Nrupa
authors: N
authors: Borkar
authors: Petrine
authors: P
authors: Wellendorph
authors: Jonas
authors: J
authors: Skovgaard-Petersen
authors: Arne
authors: A
authors: Schousboe
authors: H Steve
authors: HS
authors: White
authors: Povl
authors: P
authors: Krogsgaard-Larsen
authors: Rasmus P
authors: RP
authors: Clausen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D050485:GABA Plasma Membrane Transport Proteins / Q000187:drug effects*; D058805:GABA Uptake Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects
chemical_list: C510806:EF1502; D050485:GABA Plasma Membrane Transport Proteins; D058805:GABA Uptake Inhibitors; D007555:Isoxazoles; C490439:Slc6a12 protein, mouse