Nuclear Medicine and Biology
Volume 35, Issue 3 , Pages 315-325 , April 2008

A novel radioligand for glycine transporter 1: characterization and use in autoradiographic and in vivo brain occupancy studies

  • Zhizhen Zeng

      Affiliations

    • Imaging, Merck Research Laboratories, West Point, PA 19486, USA
    • Corresponding Author InformationCorresponding author. Imaging, WP44C-2, Merck Research Laboratories, West Point, PA 19486, USA. Tel.: +1 215 652 5627; fax: +1 215 993 6803.
    • ,
  • Julie A. O'Brien

      Affiliations

    • Sleep and Psychiatric Disorders, Merck Research Laboratories, West Point, PA 19486, USA
    • ,
  • Wei Lemaire

      Affiliations

    • Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    • ,
  • Stacey S. O'Malley

      Affiliations

    • Imaging, Merck Research Laboratories, West Point, PA 19486, USA
    • ,
  • Patricia J. Miller

      Affiliations

    • Imaging, Merck Research Laboratories, West Point, PA 19486, USA
    • ,
  • Zhijian Zhao

      Affiliations

    • Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    • ,
  • Michael A. Wallace

      Affiliations

    • Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065, USA
    • ,
  • Conrad Raab

      Affiliations

    • Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    • ,
  • Craig W. Lindsley

      Affiliations

    • Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    • Departments of Pharmacology and Chemistry, Vanderbilt University, Nashville, TN 37232, USA
    • ,
  • Cyrille Sur

      Affiliations

    • Imaging, Merck Research Laboratories, West Point, PA 19486, USA
    • ,
  • David L. Williams Jr.

      Affiliations

    • Imaging, Merck Research Laboratories, West Point, PA 19486, USA

Received 10 September 2007 ,Revised 24 October 2007 ,Accepted 5 December 2007.

References 

  1. Betz H. Ligand-gated ion channels in the brain: the amino acid receptor superfamily. Neuron. 1990;5(4):383–392
  2. Bechade C, Sur C, Triller A. The inhibitory neuronal glycine receptor. Bioessays. 1994;16(10):735–744
  3. Johnson JW, Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature. 1987;325(6104):529–531
  4. Danysz W, Parsons AC. Glycine and N-methyl-d-aspartate receptors: physiological significance and possible therapeutic applications. Pharmacol Rev. 1998;50(4):597–664
  5. Berger AJ, Dieudonne S, Ascher P. Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. J Neurophysiol. 1998;80(6):3336–3340
  6. Bergeron R, Meyer TM, Coyle JT, Greene RW. Modulation of N-methyl-d-aspartate receptor function by glycine transport. Proc Natl Acad Sci U S A. 1998;95(26):15730–15734
  7. Chen L, Muhlhauser M, Yang CR. Glycine tranporter-1 blockade potentiates NMDA-mediated responses in rat prefrontal cortical neurons in vitro and in vivo. J Neurophysiol. 2003;89(2):691–703
  8. Kinney GG, Sur C, Burno M, Mallorga PJ, Williams JB, Figueroa DJ, et al. The glycine transporter type 1 inhibitor N-[3-(4(-fluorophenyl)-3-(4(-phenylphenoxy)propyl]sarcosine potentiates NMDA receptor-mediated responses in vivo and produces an antipsychotic profile in rodent behavior. J Neurosci. 2003;23(20):7586–7591
  9. Smith KE, Borden LA, Hartig PR, Branchek T, Weinshank RL. Cloning and expression of a glycine transporter reveal colocalization with NMDA receptors. Neuron. 1992;8(5):927–935
  10. Zafra F, Aragon C, Olivares L, Danbolt NC, Gimenez C, Storm-Mathisen J. Glycine transporters are differentially expressed among CNS cells. J Neurosci. 1995;15(5 Pt 2):3952–3969
  11. Atkinson BN, Bell SC, De Vivo M, Kowalski LR, Lechner SM, Ognyanov VI, et al. ALX 5407: a potent, selective inhibitor of the hGlyT1 glycine transporter. Mol Pharmacol. 2001;60(6):1414–1420
  12. Mallorga PJ, Williams JB, Jacobson M, Marques R, Chaudhary A, Conn PJ, et al. Pharmacology and expression analysis of glycine transporter GlyT1 with [3H]-(N-[3-(4(-fluorophenyl)-3-(4(phenylphenoxy)propyl])sarcosine. Neuropharmacology. 2003;45(5):585–593
  13. Heresco-Levy U. N-Methyl-d-aspartate (NMDA) receptor-based treatment approaches in schizophrenia: the first decade. Int J Neuropsychopharmacol. 2000;3(3):243–258
  14. Tsai G, Coyle JT. Glutamatergic mechanisms in schizophrenia. Annu Rev Pharmacol Toxicol. 2002;42:165–179
  15. Le Pen G, Kew J, Alberati D, Borroni E, Heitz MP, Moreau JL. Prepulse inhibition deficits of the startle reflex in neonatal ventral hippocampal-lesioned rats: reversal by glycine and a glycine transporter inhibitor. Biol Psychiatry. 2003;54(11):1162–1170
  16. Javitt DC, Zylberman I, Zukin SR, Heresco-Levy U, Lindenmayer JP. Amelioration of negative symptoms in schizophrenia by glycine. Am J Psychiatry. 1994;151(8):1234–1236
  17. Heresco-Levy U, Javitt DC, Ermilov M, Mordel C, Horowitz A, Kelly D. Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia. Br J Psychiatry. 1996;169(5):610–617
  18. Heresco-Levy U, Javitt DC, Ermilov M, Mordel C, Silipo G, Lichtenstein M. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry. 1999;56(1):29–36
  19. Heresco-Levy U, Ermilov M, Lichtenberg P, Bar G, Javitt DC. High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia. Biol Psychiatry. 2004;55(2):165–171
  20. Tsai G, Yang P, Chung LC, Lange N, Coyle JT. d-serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. 1998;44(11):1081–1089
  21. Tsai G, Lane HY, Yang P, Chong MY, Lange N. Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. 2004;55(5):452–456
  22. Vandenberg RJ, Aubrey KR. Glycine transport inhibitors as potential antipsychotic drugs. Expert Opin Ther Targets. 2001;5(4):507–518
  23. Lindsley CW, Zhao Z, Leister WH, O'Brien J, Lemaire W, Williams DL, et al. Design, synthesis, and in vivo efficacy of glycine transporter–1 (GlyT1) inhibitors derived from a series of [4-phenyl-1-(propylsulfonyl)piperidin-4-yl]methyl benzamides. Chem Med Chem. 2006;1(8):807–811
  24. Limbird LE. Cell surface receptors: a short course on theory and methods. Boston: Martinus Nijhoff Publishing; 1986;
  25. Zhao Z, O'Brien JA, Lemaire W, Williams DL, Jacobson MA, Sur C, et al. Synthesis and SAR of GlyT1 inhibitors derived from a series of N-((4-(morpholine-4-carbonyl)-1-(propylsulfonyl)piperidin-4-yl)methyl)benzamides. Bioorg Med Chem Lett. 2006;16(23):5968–5972
  26. Hayden T, Ravert WBM, Klitenick MA, Wong DF, Dannals RF. Radiosynthesis of ligand for studying the glycine transporter: [11C]ALX-5407. J Labelled Compd Radiopharm. 2001;44:241–246
  27. Lowe JA, Drozda SE, Fisher K, Strick C, Lebel L, Schmidt C, et al. [3H]-(R)-NPTS, a radioligand for the type 1 glycine transporter. Bioorg Med Chem Lett. 2003;13(7):1291–1292
  28. Adams RH, Sato K, Shimada S, Tohyama M, Puschel AW, Betz H. Gene structure and glial expression of the glycine transporter GlyT1 in embryonic and adult rodents. J Neurosci. 1995;15(3 Pt 2):2524–2532
  29. Jursky F, Tamura S, Tamura A, Mandiyan S, Nelson H, Nelson N. Structure, function and brain localization of neurotransmitter transporters. J Exp Biol. 1994;196:283–295
  30. Cubelos B, Gimenez C, Zafra F. Localization of the GLYT1 glycine transporter at glutamatergic synapses in the rat brain. Cereb Cortex. 2005;15(4):448–459
  31. Danglot L, Rostaing P, Triller A, Bessis A. Morphologically identified glycinergic synapses in the hippocampus. Mol Cell Neurosci. 2004;27(4):394–403
  32. Atack JR, Pike A, Clarke A, Cook SM, Sohal B, McKernan RM, et al. Rat pharmacokinetics and pharmacodynamics of a sustained release formulation of the GABAA alpha5-selective compound L-655,708. Drug Metab Dispos. 2006;34(5):887–893
  33. Li J, Fish RL, Cook SM, Tattersall FD, Atack JR. Comparison of in vivo and ex vivo [3H]flumazenil binding assays to determine occupancy at the benzodiazepine binding site of rat brain GABAA receptors. Neuropharmacology. 2006;51(1):168–172
  34. Assie MB, Dominguez H, Consul-Denjean N, Newman-Tancredi A. In vivo occupancy of dopamine D2 receptors by antipsychotic drugs and novel compounds in the mouse striatum and olfactory tubercles. Naunyn Schmiedebergs Arch Pharmacol. 2006;373(6):441–450
  35. Wee S, Carroll FI, Woolverton WL. A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants. Neuropsychopharmacology. 2006;31(2):351–362
  36. Atack JR, Scott-Stevens P, Beech JS, Fryer TD, Hughes JL, Cleij MC, et al. Comparison of lorazepam [7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one] occupancy of rat brain gamma-aminobutyric acid(A) receptors measured using in vivo [3H]flumazenil (8-fluoro 5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid ethyl ester) binding and [11C]flumazenil micro-positron emission tomography. J Pharmacol Exp Ther. 2007;320(3):1030–1037

PII: S0969-8051(07)00305-8

doi: 10.1016/j.nucmedbio.2007.12.002

Nuclear Medicine and Biology
Volume 35, Issue 3 , Pages 315-325 , April 2008

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