Glycine transporter-1: A new potential therapeutic target for schizophrenia

Current Pharmaceutical Design

Volumn 17, Issue 2, 2011, Pages 112-120

  Hashimoto, Kenji ^a  

^a CHIBA UNIVERSITY   (Japan)

Author keywords

Glia; Glutamate; Glycine; Nmda receptor; Schizophrenia; Transporter

Indexed keywords

2 AMINO 6 CHLORO N [1 [4 PHENYL 1 (PROPYLSULFONYL)PIPERIDIN 4 YL]ETHYL]BENZAMIDE; 2 CHLORO N [ALPHA (2 PIPERIDINYL)BENZYL] 3 TRIFLUOROMETHYLBENZAMIDE; 2 METHOXY N [1 [4 PHENYL 1 (PROPYLSULFONYL)PIPERIDIN 4 YL]METHYL]BENZAMIDE; 4 (4 [[2 (CYCLOPROPYLMETHOXY) 5 (METHYLSULFONYL)PHENYL]CARBONYL]PIPERAZIN 1 YL) 3 FLUOROBENZONITRILE; 4 [5 CHLORO 2 (4 METHOXY PHENYLSULFANYL)PHENYL] 2 METHYLPIPERAZIN 1 YL ACETIC ACID; CLOZAPINE; DEXTRO SERINE; DIZOCILPINE; DOPAMINE; GLYCINE TRANSPORTER 1; GSK 931145; N [2 (ACEPAN 1 YL) 2 (2 METHOXYPHENYLETHYL) 4 TRIFLUOROMETHYLBENZENESULFONAMIDE; N [2 (ACEPAN 1 YL) 2 PHENYLETHYL]BENZENESULFONAMIDE; N [3 (4 FLUOROPHENYL) 3 (4 PHENYLPHENOXY)PROPYL]SARCOSINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N METHYL N [(4 TRIFLUOROMETHYL)PHENOXY] 3 PHENYL PROPYLGLYCINE; NEUROLEPTIC AGENT; ORG 24461; ORG 24598; ORG 25935; PF 3463275; R 231857; RADIOPHARMACEUTICAL AGENT; RG 1678; RISPERIDONE; RO 4840700; SARCOSINE; SSR 103800; UNCLASSIFIED DRUG;

ARTICLE; BRAIN SCINTISCANNING; COGNITION; DEPRESSION; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG PENETRATION; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; ENZYME INHIBITION; HUMAN; NEUROTRANSMISSION; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; QUALITY OF LIFE; SCHIZOPHRENIA;

ANIMALS; ANTIPSYCHOTIC AGENTS; CLINICAL TRIALS, PHASE II AS TOPIC; GLYCINE; GLYCINE PLASMA MEMBRANE TRANSPORT PROTEINS; HUMANS; MICE; RATS; RECEPTORS, N-METHYL-D-ASPARTATE; SARCOSINE; SCHIZOPHRENIA; SYNAPTIC TRANSMISSION;

EID: 79953316447     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161211795049598     Document Type: Article

References (94)

1. Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 1991; 148: 1301-08.
2. Olney JW, Farber NB. Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry 1995; 52: 998-1007.
3. Coyle JT. The glutamatergic dysfunction hypothesis for schizophrenia. Harv Rev Psychiatry 1996; 3: 241-53.
4. Krystal JH, D'Souza DC, Petrakis IL, et al. NMDA agonists and antagonists as probes of glutamatergic dysfunction and pharmacotherapies in neuropsychiatric disorders. Harv Rev Psychiatry 1999; 7: 125-43.
5. Goff DC, Coyle JT. The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry 2001; 158: 1367-77.
6. Coyle JT, Tsai G. The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophrenia. Psychopharmacol 2004; 174: 32-8.
7. Hashimoto K, Fukushima T, Shimizu E, et al. Decreased serum levels of D-serine in patients with schizophrenia: evidence in support of the NMDA receptor hypofunction hypothesis of schizophrenia. Arch Gen Psychiatry 2003; 60: 572-6.
8. Hashimoto K, Okamura N, Shimizu E, Iyo M. Glutamate hypothesis of schizophrenia and approach for possible therapeutic drugs. Curr Med Chem - CNS Agents 2004; 4: 147-54.
9. Hashimoto K, Shimizu E, Iyo M. Dysfunction of glia-neuron communication in pathophysiology of schizophrenia. Curr Psychiatry Rev 2005; 1: 151-63.
10. Hashimoto K. The NMDA receptor hypofunction hypothesis for schizophrenia and glycine modulatory sites on the NMDA receptors as potential therapeutic drugs. Clin Psychopharmacol Neurosci 2006; 4: 3-10.
11. Luby ED, Cohen BD, Rosenbaum G, Gottlieb JS, Kelley R. Study of a new schizophrenomimetic drug; sernyl. AMA Arch Neurol Psychiatry 1959; 81: 363-9.
12. Allen RM, Young SJ. Phencyclidine-induced psychosis. Am J Psychiatry 1978; 135: 1081-4.
13. Krystal JH, Karper LP, Seibyl JP, et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 1994; 51: 199-214.
14. Malhotra AK, Pinals DA, Weingartner H, et al. NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Neuropsychopharmacology 1996; 14: 301-7.
15. Hartvig P, Valtysson J, Lindner KJ, et al. Central nervous system effects of subdissociative doses of (S)-ketamine are related to plasma and brain concentrations measured with positron emission tomography in healthy volunteers. Clin Pharmacol Ther 1995; 58: 165-73.
16. Lahti AC, Koffel B, LaPorte D, Tamminga CA. Subanesthetic doses of ketamine stimulate psychosis in schizophrenia. Neuropsychopharmacology 1995; 13: 9-19.
17. Aragon C, Lopez-Corcuera B. Glycine transporters: crucial roles of pharmacological interest revealed by gene deletion. Trends Pharmacol Sci 2005; 26: 283-6.
18. Eulenburg V, Armsen W, Betz H, Gomeza J. Glycine transporters: essential regulators of neurotransmission. Trends Biochem Sci 2005; 30: 325-33.
19. Raiteri L, Raiteri M. Functional 'glial' GLYT1 glycine transporters expressed in neurons. J Neurochem 2010; 114: 647-53.
20. Heresco-Levy U, Javitt DC. Comparative effects of glycine and Dcycloserine on persistent negative symptoms in schizophrenia: a retrospective analysis. Schizophrenia Res 2004; 66: 89-96.
21. 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): 3952-9.
22. Zafra F, Gomeza J, Olivares L, Aragon C, Gimenez C. Regional distribution and developmental variation of the glycine transporters GLYT1 and GLYT2 in the rat CNS. Eur J Neurosci 1995; 7: 1342-52.
23. Cubelos B, Gimenez C, Zafra F. Localization of the GLYT1 glycine transporter at glutamatergic synapses in the rat brain. Cereb Cortex 2005; 15: 448-59.
24. Bergeron R, Meyer TM, Coyle JT, Greene RW. Modulation of Nmethyl-D-aspartate receptor function by glycine transport. Proc Natl Acad Sci USA 1998; 95: 15730-4.
25. Gomeza J, Hulsmann S, Ohno K, Eulenburg V, Szoke K, Richter D, Betz H. Inactivation of the glycine transporter 1 gene discloses vital role of glial glycine uptake in glycinergic inhibition. Neuron 2003; 40: 785-96.
26. Tsai G, Ralph-Williams RJ, Martina M, Bergeron R, Berger-Sweeney J, Dunham KS, Jiang Z, Caine SB, Coyle JT. Gene knockout of glycine transporter 1: characterization of the behavioral phenotype. Proc Natl Acad Sci USA 2004; 101: 8485-90.
27. Vandenberg RJ, Aubrey KR. Glycine transport inhibitors as potential antipsychotic drugs. Expert Opin Ther Targets 2001; 5: 507-18.
28. Sur C, Kinney GG. The therapeutic potential of glycine transporter-1 inhibitors. Expert Opin Investig Drugs 2004; 13: 515-21.
29. Kinney GG, Sur C. Glycine site modulators and glycine transporter-1 inhibitors as novel therapeutic targets for the treatment of schizophrenia. Curr Neuropsychopharmacol 2005; 3: 35-43.
30. Hashimoto K. Glycine transporter inhibitors as therapeutic agents for schizophrenia. Recent Pat CNS Drug Discov 2006; 1: 43-54.
31. Lechner SM. Glutamate-based therapeutic approaches: inhibitors of glycine transport. Curr Opin Pharmacol 2006; 6: 75-81.
32. Lindsley CW, Wolkenberg SE, Kinney GG. Progress in the preparation and testing of glycine transporter type-1 (GlyT-1) inhibitors. Curr Top Med Chem 2006; 6: 1883-96.
33. Hashimoto K. Glycine transporter-1 inhibitors as novel therapeutic drugs for schizophrenia. Cent Nerv Syst Agents Med Chem 2007; 7: 177-82.
34. Javitt DC. Glycine transport inhibitors and the treatment of schizophrenia. Biol Psychiatry 2008; 63: 6-8.
35. Yang CR, Svensson KA. Allosteric modulation of NMDA receptor via elevation of brain glycine and D-serine: the therapeutic potentials for schizophrenia. Pharmacol Ther 2008; 120: 317-32.
36. Javitt DC. Glycine transport inhibitors for the treatment of schizophrenia: symptom and disease modification. Curr Opin Drug Discov Devel 2009; 12: 468-78.
37. Wolkenberg SE, Sur C. Recent progress in the discovery of nonsarcosine based GlyT1 inhibitors. Curr Top Med Chem 2010; 10: 170-86.
38. Hashimoto K. Glycine transport inhibitors for the treatment of schizophrenia. Open Med Chem J 2010; 4: 10-9.
39. Hashimoto K. Chapter 14. Glycine transporter inhibitors as therapeutic agents for schizophrenia. In: Frontiers in CNS Drug Discovery (Volume 1), ed. Choudhary MI and Rahman A, Bentham Science Publishers, 2010; 1: pp.284-303.
40. Hashimoto K. Sarcosine and decreased risk for prostate cancer in schizophrenia. Open Clin Chem J 2009; 2: 22-3.
41. 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: 452-6.
42. Lane HY, Huang CL, Wu PL, et al. Glycine transporter 1 inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophrenia. Biol Psychiatry 2006; 60: 645-9.
43. Lane HY, Chang YC, Liu YC, Chiu CC, Tsai GE. Sarcosine or Dserine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study. Arch Gen Psychiatry 2005; 62: 1196-204.
44. Lane HY, Liu YC, Huang CL, et al. Sarcosine (N-methylglycine) treatment for acute schizophrenia: a randomized, double-blind study. Biol Psychiatry 2008; 63: 9-12.
45. Lane HY, Lin CH, Huang YJ, Liao CH, Chang YC, Tsai GE. A randomized, double-blind, placebo-controlled comparison study of sarcosine (N-methylglycine) and D-serine add-on treatment for schizophrenia. Int J Neuropsychopharmacol 2010; 13: 451-60.
46. Zhang HX, Hyrc K, Thio LL. The glycine transport inhibitor sarcosine is an NMDA receptor co-agonist that differs from glycine. J Physiol 2009; 587: 3207-20.
47. Atkinson BN, Bell SC, De Vivo M, et al. ALX 5407: a potent, selective inhibitor of the hGlyT-1 glycine transporter. Mol Pharmacol 2001; 60: 1414-20.
48. Aubrey KR, Vandenberg RJ. N-[3-(4'-fluorophenyl)-3-(4'- phenylphenoxy)propyl] sarcosine (NFPS) is a selective persistent inhibitor of glycine transport. Br J Pharmacol 2001; 134: 1429-36.
49. Jentsch JD, Roth RH. The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 1999; 20: 201-25.
50. Hashimoto K, Fujita Y, Shimizu E, Iyo M. Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of clozapine, but not haloperidol. Eur J Pharmacol 2005; 519: 114-7.
51. Hashimoto K, Fujita Y, Ishima T, Chaki S, Iyo M. Phencyclidineinduced cognitive deficits in mice are improved by subsequent subchronic administration of glycine transporter-1 inhibitor NFPS and D-serine. Eur Neuropsychopharmacol 2008; 18: 414-21.
52. Kinney GG, Sur C, Burno M, 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: 7586-91.
53. Lipina T, Labrie V, Weiner I, Roder J. Modulators of the glycine site on NMDA receptors, D-serine and ALX 5407, display similar beneficial effects to clozapine in mouse models of schizophrenia. Psychopharmacology (Berl) 2005; 179: 54-67.
54. Karasawa J, Hashimoto K, Chaki S. D-serine and a glycine transporter inhibitor improve MK-801-induced cognitive deficits in a novel object recognition test in rats. Behav Brain Res 2008; 186: 78-83.
55. Manahan-Vaughan D, Wildforster V, Thomson C. Rescue of hippocampal LTP and learning deficits in a rat model of psychosis by inhibition of glycine transporter-1 (GlyT-1). Eur J Neurosci 2008; 28: 1342-50.
56. Shimazaki T, Kaku A, Chaki S. D-Serine and a glycine transporter-1 inhibitor enhance social memory in rats. Psychopharmacology (Berl.) 2010; 209: 263-70.
57. Harsing LG Jr, Gacsalyi I, Szabo G, et al. The glycine transporter-1 inhibitors NFPS and ORG24461: a pharmacological study. Pharmacol Biochem Behav 2003; 74: 811-25.
58. Nagy K, Marko B, Zsilla G, et al. Alterations in brain extracellular dopamine and glycine levels following combined administration of the glycine transporter type-1 inhibitor Org-24461 and risperidone. Neurochem Res 2010; 35: 2096-106.
59. Brown A, Carlyle I, Clark J, et al. Discovery and SAR of Org24598 - a selective glycine uptake inhibitor. Bioorg Med Chem Lett 2001; 11: 2007-9.
60. 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: 1162-70.
61. Ge J, Hamilton W, Shahid M, Hill DR, Walker G. The effects of Org25935 on the extracellular levels of glycine in brain regions of freely moving rats. Brit J Pharmacol 2001; 133: 135p.
62. Depoortere R, Dargazanli G, Estenne-Bouhtou G, et al. Neurochemical, electrophysiological and pharmacological profiles of the selective inhibitor of the glycine transporter-1 SSR504734, a potential new type of antipsychotic. Neuropsychopharmacology 2005; 30: 1963-85.
63. Leonetti M, Desvignes C, Bougault I, Souilhac J, Oury-Donat F, Steinberg R. 2-Chloro-N-[(S)-phenyl [(2S)-piperidin-2-yl] methyl]-3-trifluoromethyl benzamide, monohydrochloride, an inhibitor of the glycine transporter type 1, increases evoked-dopamine release in the rat nucleus accumbens in vivo via an enhanced glutamatergic neurotransmission. Neuroscience 2006; 137: 555-64.
64. Harich S, Gross G, Bespalov A. Stimulation of the metabotropic glutamate 2/3 receptor attenuates social novelty discrimination deficits induced by neonatal phencyclidine treatment. Psychopharmacology (Berl) 2007; 192: 511-9.
65. Gozzi A, Herdon H, Schwarz A, et al. Pharmacological stimulation of NMDA receptors via co-agonist site suppresses fMRI response to phencyclidine in the rat. Psychopharmacology (Berl) 2008; 201: 273-84.
66. Black MD, Varty GB, Arad M, et al. Procognitive and antipsychotic efficacy of glycine transport 1 inhibitors (GlyT1) in acute and neurodevelopmental models of schizophrenia: latent inhibition studies in the rat. Psychopharmacology (Berl) 2009; 202: 385-96
67. Singer P, Feldon J, Yee BK. Interactions between the glycine transporter 1 (GlyT-1) inhibitor SSR504734 and psychoactive drugs in mouse motor behaviour. Eur Neuropsychopharmacol 2009; 19: 571-80.
68. Alberati D, Moreau JL, Mory R, Pinard E, Wettstein JG. Pharmacological evaluation of a novel assay for detecting glycine transporter 1 inhibitors and their antipsychotic potential. Pharmacol Biochem Behav 2010; 97: 185-91.
69. Boulay D, Pichat P, Dargazanli G, et al. Characterization of SSR103800, a selective inhibitor of the glycine transporter-1 in models predictive of therapeutic activity in schizophrenia. Pharmacol Biochem Behav 2008; 91: 47-58.
70. Boulay D, Bergis O, Avenet P, Griebel G. The glycine transporter-1 inhibitor SSR103800 displays a selective and specific antipsychotic-like profile in normal and transgenic mice. Neuropsychopharamacology 2010; 35: 416-27.
71. Lindsley CW, Zhao Z, Leister WH, et al. Design, synthesis, and in vivo efficacy of glycine transporter-1 (GlyT-1) inhibitors derived from a series of [4-phenyl-1-(propylsulfonyl)piperidin-4-yl]methyl benzamides. Chem Med Chem 2006; 1: 807-11.
72. Zhao Z, O'Brien JA, Lemaire W, et al. Synthesis and SAR of GlyT-1 inhibitors derived from a series of N-((4-(morpholine-4-carbonyl)-1-(propylsulfonyl)piperidin-4-yl)methyl)benzamids. Bioorg Med Chem Lett 2006; 16: 5968-72.
73. Pinard E, Ceccarelli SM, Stalder H, Alberati D. Discovery of N-(2-aryl-cyclohexyl) substituted spiropiperidines as a novel class of GlyT-1 inhibitors. Bioorg Med Chem Lett 2006; 16: 349-53.
74. Ceccarelli SM, Pinard E, Stalder H, Alberati D. Discovery of N-(2-hydroxy-2-aryl-cyclohexyl) substituted spiropiperidines as GlyT-1 antagonists with improved pharmacological profile. Bioorg Med Chem Lett 2006; 16: 354-7.
75. Alberati D, Hainzl D, Jolidon S, Krafft EA, Kurt A, Maier A, Pinard E, Thomas AW, Zimmerli D. Discovery of 4-substituted-8-(2-hydroxy-2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of highly selective GlyT-1 inhibitors with improved metabolic stability. Bioorg Med Chem Lett 2006; 16: 4311-5.
76. Alberati D, Ceccarelli SM, Jolidon S, et al. Design and synthesis of 4-substituted-8-(2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of GlyT-1 inhibitors: achieving selectivity against the mu opioid and nociceptin/orphanin FQ peptide (NOP) receptors. Bioorg Med Chem Lett 2006; 16: 4305-10.
77. Alberati D, Hainzl D, Jolidon S, et al. 4-Substituted-8-(1-phenylcyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of highly selective GlyT-1 inhibitors with superior pharmacological and pharmacokinetic parameters. Bioorg Med Chem Lett 2006; 16: 4321-5.
78. Pinard E, Alberati D, Borroni E, et al. Discovery of benzoylpiperazines as a novel class of potent and selective GlyT1 inhibitors. Bioorg Med Chem Lett 2008; 18: 5134-9.
79. Pinard E, Alanine A, Alberati D, et al. Sective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2- yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1- methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia. J Med Chem 2010; 53: 4603-14.
80. Smith G, Ruhland T, Mikkelsen G, et al. The synthesis and SAR of 2-arylsulfanyl-phenyl piperazinyl acetic acids as GlyT-1 inhibitors. Bioorg Med Chem Lett 2004; 14: 4027-30.
81. Smith G, Mikkelsen G, Eskildsen J, Bundgaard C. The synthesis and SAR of 2-arylsulfanylphenyl-1-oxyalkylamino acids as GlyT-1 inhibitors. Bioorg Med Chem Lett 2006; 16: 3981-4.
82. Lowe JA 3rd, Hou X, Schmidt C, et al. The discovery of a structurally novel class of inhibitors of the type 1 glycine transporter. Bioorg Med Chem Lett 2009; 19: 2974-6.
83. Roberts BM, Shaffer CL, Seymour PA, Schmidt CJ, Williams GV, Castner SA. Glycine transporter inhibition reverses ketamineinduced working memory deficits. Neuroreport 2010; 21: 390-4.
84. ClinicalTrials.gov [homepage on the Internet]. A study of PF-03463275 as add-on therapy in outpatients with persistent negative symptoms of schizophrenia. [updated: October 12, 2010]. http://www.clinicaltrials.gov/ct2/show/NCT00977522?term=PF-03463275&rank=2
85. Lowe JA 3rd, Deninno SL, Drozda SE, et al. An octahydrocyclopenta[ c]pyrrole series of inhibitors of the type 1 glycine transporter. Biorg Med Chem Lett 2010; 20: 907-11.
86. Varnes JG, Forst JM, Hoerter TN, et al. Identification of N-(2-(azepan-1-yl)-2-phenylethyl)-benzenesulfonamides as novel inhibitors of GlyT1. Biorg Med Chem Lett 2010; 20: 4878-81.
87. Liem-Moolenaar M, Zoethout R, de Boer P, et al. The effects of a glycine reuptake inhibitor R231857 on the central nervous system and on scopolamine-induced impairments in cognitive and psychomotor function in healthy subjects. J Psychopharmacol 2010; 24: 1681-7.
88. Roche Global Web Site [Homepage on the Internet]. Roche reports positive Phase II results with potential first-in-class treatment for the negative symptoms of schizophrenia. [Basel, November 10, 2009]. http://www.roche.com/investors/ir_update/inv-update-2009-11-10.htm
89. Roche Global Web Site [Homepage on the Internet]. Phase II study with first-in-class investigational drug demonstrates improvement in negative symptoms in patients with schizophrenia. [Basel, December 6, 2010]. http://www.roche.com/investors/ir_update/invupdate-2010-12-06b.htm
90. Lindsley C. GlyT1 - Up from the Ashes. The importance of not condemning a mechanisms base on a single chemotype. ACS Chem Neurosci 2010; 1: 165-6.
91. Williams DL, Jennings A, Lewis R, et al. A novel glycine transporter-1 PET tracer: from discovery to clinic. Abstr Neurosci 2008; 885.15.
92. Passchier J, Gentile G, Porter R, et al. Identification and evaluation of [11C]GSK 931145 as a novel ligand for imaging the type 1 glycine transporter with positron emission tomography. Synapse 2010; 64: 542-9.
93. 11C-GSK931145 determined from primate and human whole-body PET. Mol Imaging Biol in press.
94. Toyohara J, Ishiwata K, Sakata M, et al. In vivo evaluation of cabon-11 labelled non-sarcosine-based glycine transporter 1 inhibitors in mice and conscious monkeys. Nuc Med Biol in press.