Nailing the Right Dose! The Key for Developing Glycine Transporter Inhibitors for Schizophrenia

  • Daniel Umbricht
    Address correspondence to Daniel Umbricht, M.D., Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Building 1, Room 16.N655, Grenzacherstrasse 124, 4070 Basel, Switzerland.
    Roche Pharmaceutical Research and Early Development, Roche Innovation Center, Basel, Switzerland
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        • D’Souza D.C.
        • Carson R.E.
        • Driesen N.
        • Johannesen J.
        • Ranganathan M.
        • Krystal J.H.
        • and the Yale GlyT1 Study Group
        Dose-related target occupancy and effects on circuitry, behavior, and neuroplasticity of the glycine transporter-1 inhibitor PF-03463275 in healthy and schizophrenia subjects.
        Biol Psychiatry. 2018; 84: 413-421
        • Teyler T.J.
        • Hamm J.P.
        • Clapp W.C.
        • Johnson B.W.
        • Corballis M.C.
        • Kirk I.J.
        Long-term potentiation of human visual evoked responses.
        Eur J Neurosci. 2005; 21: 2045-2050
        • McNair N.A.
        • Clapp W.C.
        • Hamm J.P.
        • Teyler T.J.
        • Corballis M.C.
        • Kirk I.J.
        Spatial frequency-specific potentiation of human visual-evoked potentials.
        Neuroreport. 2006; 17: 739-741
        • Umbricht D.
        • Alberati D.
        • Martin-Facklam M.
        • Borroni E.
        • Youssef E.A.
        • Ostland M.
        • et al.
        Effect of bitopertin, a glycine reuptake inhibitor, on negative symptoms of schizophrenia: A randomized, double-blind, proof-of-concept study.
        JAMA Psychiatry. 2014; 71: 637-646
        • Dunayevich E.
        • Buchanan R.W.
        • Chen C.Y.
        • Yang J.
        • Nilsen J.
        • Dietrich J.M.
        • et al.
        Efficacy and safety of the glycine transporter type-1 inhibitor AMG 747 for the treatment of negative symptoms associated with schizophrenia.
        Schizophr Res. 2017; 182: 90-97
        • Schoemaker J.H.
        • Jansen W.T.
        • Schipper J.
        • Szegedi A.
        The selective glycine uptake inhibitor org 25935 as an adjunctive treatment to atypical antipsychotics in predominant persistent negative symptoms of schizophrenia: Results from the GIANT trial.
        J Clin Psychopharmacol. 2014; 34: 190-198
        • Martin-Facklam M.
        • Pizzagalli F.
        • Zhou Y.
        • Ostrowitzki S.
        • Raymont V.
        • Brasic J.R.
        • et al.
        Glycine transporter type 1 occupancy by bitopertin: A positron emission tomography study in healthy volunteers.
        Neuropsychopharmacology. 2013; 38: 504-512
        • Martina M.
        • Gorfinkel Y.
        • Halman S.
        • Lowe J.A.
        • Periyalwar P.
        • Schmidt C.J.
        • et al.
        Glycine transporter type 1 blockade changes NMDA receptor-mediated responses and LTP in hippocampal CA1 pyramidal cells by altering extracellular glycine levels.
        J Physiol. 2004; 557: 489-500
        • Nong Y.
        • Huang Y.Q.
        • Ju W.
        • Kalia L.V.
        • Ahmadian G.
        • Wang Y.T.
        • et al.
        Glycine binding primes NMDA receptor internalization.
        Nature. 2003; 422: 302-307
        • Fraguas D.
        • Diaz-Caneja C.M.
        • Pina-Camacho L.
        • Umbricht D.
        • Arango C.
        Predictors of placebo response in pharmacological clinical trials of negative symptoms in schizophrenia: A meta-regression analysis.
        Schizophr Bull. 2018; ([published online ahead of print Jan 19])

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