Author/Authors :
Garrick Smith، نويسنده , , Thomas Ruhland، نويسنده , , Gitte Mikkelsen، نويسنده , , Kim Andersen، نويسنده , , Claus Tornby Christoffersen، نويسنده , , Lene Hjorth Alifrangis، نويسنده , , Kjell Arne Mork، نويسنده , , Stephen P Wren، نويسنده , , Neil Harris، نويسنده , , Barry M Wyman، نويسنده , , Guillaume Brandt، نويسنده ,
Abstract :
Elevation of glycine levels and activation of the NMDA receptor by inhibition of the glycine transporter 1 (GlyT-1) is a potential strategy for the treatment of schizophrenia. A novel series of GlyT-1 inhibitors have been identified containing the 2-arylsulfanyl-phenylpiperazine motif. The most prominent member of this series, (R)-4-[5-chloro-2-(4-methoxy-phenylsulfanyl)-phenyl]-2-methyl-piperazin-1-yl-acetic acid (31) is a potent glycine transporter-1 inhibitor (IC50=150 nM), which elevated glycine levels in rat ventral hippocampus as measured by microdialysis in vivo at doses of 1.2–4.6 mg/kg s.c.
