Selective mGAT2 (BGT-1) GABA Uptake Inhibitor: Design, synthesis and pharmacological characterization

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Stine Byskov Vogensen, Lars Jørgensen, Karsten Kirkegaard Madsen, Nrupa Nitin Borkar, Petrine Wellendorph, Jonas Skovgaard-Petersen, Arne Schousboe, H. Steve White, Povl Krogsgaard-Larsen, Rasmus Prætorius Clausen

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.
OriginalsprogEngelsk
TidsskriftJournal of Medicinal Chemistry
Vol/bind56
Tidsskriftsnummer5
Sider (fra-til)2160-2164
Antal sider5
DOI
StatusUdgivet - 11 feb. 2013

ID: 45807862