Targeting of NMDA Receptors in the treatment of major depression

Current Pharmaceutical Design

Volumn 20, Issue 32, 2014, Pages 5151-5159

  Dang, Yong Hui ^a   Ma, Xian Cang ^b   Zhang, Ji Chun ^c   Ren, Qian ^c   Wu, Jin ^c   Gao, Cheng Ge ^b   Hashimoto, Kenji ^c  

^a MEDICAL SCHOOL OF XI AN JIAOTONG UNIVERSITY   (China)

^b THE FIRST AFFILIATED HOSPITAL OF XI AN JIAOTONG UNIVERSITY   (China)

^c CHIBA UNIVERSITY   (Japan)

Author keywords

Depression; GluN2B subtype; Glutamate; Ketamine; NMDA receptors; Treatment resistant

Indexed keywords

4 BENZYL ALPHA (4 HYDROXYPHENYL) BETA METHYL 1 PIPERIDINEPROPANOL; ANTIDEPRESSANT AGENT; CYCLOSERINE; GLUTAMIC ACID; GLYCINE TRANSPORTER 1; KETAMINE; LANICEMINE; MEMANTINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; RAPASTINEL; SARCOSINE; TRAXOPRODIL;

ANTIDEPRESSANT ACTIVITY; ARTICLE; BRAIN LEVEL; CENTRAL NERVOUS SYSTEM; CEREBROSPINAL FLUID LEVEL; DRUG TARGETING; HIPPOCAMPUS; HUMAN; MAJOR DEPRESSION; NONHUMAN; PATHOPHYSIOLOGY; PREFRONTAL CORTEX; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; ANIMAL; ANTAGONISTS AND INHIBITORS; DEPRESSIVE DISORDER, MAJOR; DRUG RESISTANCE; METABOLISM; MOLECULARLY TARGETED THERAPY; TIME;

ANIMALS; ANTIDEPRESSIVE AGENTS; DEPRESSIVE DISORDER, MAJOR; DRUG RESISTANCE; HUMANS; KETAMINE; MOLECULAR TARGETED THERAPY; RECEPTORS, N-METHYL-D-ASPARTATE; TIME FACTORS;

EID: 84905560244     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612819666140110120435     Document Type: Article

References (137)

1. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003; 289: 3095-105.
2. Nestler EJ, Barrot M, DiLeone RJ, et al. Neurobiology of depression. Neuron 2002; 34: 13-25.
3. Murrough JW. Ketamine as a novel antidepressant: from synapse to behavior. Clin Pharmacol Ther 2012; 91: 303-9.
4. Ressler KJ, Nemeroff CB. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety 2000; 12 (Suppl 1): 2-19.
5. Renard CE, Fiocco AJ, Clenet F, Hascoet M, Bourin M. Is dopamine implicated in the antidepressant-like effects of selective serotonin reuptake inhibitors in the mouse forced swimming test? Psychopharmacology (Berl) 2001; 159: 42-50.
6. Hyman SE, Nestler EJ. Initiation and adaptation: a paradigm for understanding psychotropic drug action. Am J Psychiatry 1996; 153: 151-62.
7. Klak K, Palucha A, Branski P, Sowa M, Pilc A. Combined administration of PHCCC, a positive allosteric modulator of mGlu4 receptors and ACPT-I, mGlu III receptor agonist evokes antidepressant-like effects in rats. Amino Acids 2007; 32: 169-72.
8. Krystal JH. Ketamine and the potential role for rapid-acting antidepressant medications. Swiss Med Wkly 2007; 137: 215-6.
9. Maeng S, Zarate CA Jr. The role of glutamate in mood disorders: results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects. Curr Psychiatry Rep 2007; 9: 467-74.
10. Pilc A, Chaki S, Nowak G, Witkin JM. Mood disorders: regulation by metabotropic glutamate receptors. Biochem Pharmacol 2008; 75: 997-1006.
11. Pittenger C, Sanacora G, Krystal JH. The NMDA receptor as a therapeutic target in major depressive disorder. CNS Neurol. Disord Drug Targets 2007; 6: 101-15.
12. Swanson CJ, Bures M, Johnson MP, et al. Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nat Rev Drug Discov 2005; 4: 131-44.
13. Sen S, Sanacora G. Major depression: emerging therapeutics. Mt Sinai J Med 2008; 75: 204-25.
14. Witkin JM, Marek GJ, Johnson BG, Schoepp DD. Metabotropic glutamate receptors in the control of mood disorders. CNS Neurol Disord Drug Targets 2007; 6: 87-100.
15. Hashimoto K. Emerging role of glutamate in the pathophysiology of major depressive disorder. Brain Res Rev 2009; 61: 105-23.
16. Hashimoto K. The role of glutamate on the action of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 1558-68.
17. Tokita K, Yamaji T, Hashimoto K. Roles of glutamate signaling in preclinical and/or mechanistic models of depression. Pharmacol Biochem Behav 2012; 100: 688-704.
18. Monaghan DT, Bridges RJ, Cotman CW. The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. Annu Rev Pharmacol Toxicol 1989; 29: 365-402.
19. Seeburg PH. The TiPS/TINS lecture: the molecular biology of mammalian glutamate receptor channels. Trends Pharmacol Sci 1993; 14: 297-303.
20. Young AB, Fagg GE. Excitatory amino acid receptors in the brain: membrane binding and receptor autoradiographic approaches. Trends Pharmacol Sci 1990; 11: 126-33.
21. Traynelis SF, Wollmuth LP, McBain CJ, et al. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 2010; 62: 405-96.
22. Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor ion channels. Pharmacol Rev 1999; 51: 7-61.
23. Paoletti P, Neyton J. NMDA receptor subunits: function and pharmacology. Curr Opin Pharmacol 2007; 7: 39-47.
24. Stephenson FA. Structure and trafficking of NMDA and GABAA receptors. Biochem Soc Trans 2006; 34: 877-81.
25. Monyer H, Sprengel R, Schoepfer R, et al. Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 1992; 256: 1217-21.
26. Nakanishi S. Molecular diversity of glutamate receptors and implications for brain function. Science 1992; 258: 597-603.
27. Madden DR. The structure and function of glutamate receptor ion channels. Nat Rev Neurosci 2002; 3: 91-101.
28. Myers SJ, Dingledine R, Borges K. Genetic regulation of glutamate receptor ion channels. Annu Rev Pharmacol Toxicol 1999; 39: 221-41.
29. Sucher NJ, Awobuluyi M, Choi YB, Lipton SA. NMDA receptors: from genes to channels. Trends Pharmacol Sci 1996; 17: 348-55.
30. Loftis JM, Janowsky A. The N-methyl-D-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications. Pharmacol Ther 2003; 97: 55-85.
31. Campbell S, Macqueen G. The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci 2004; 29: 417-26.
32. Ho Y, Liu T, Tai M, et al. Effects of olfactory bulbectomy on NMDA receptor density in the rat brain. Brain Res., 2001; 900: 214-8.
33. Robichaud M, Beauchemin V, Lavoie N, Dennis T, Debonnel G. Effects of bilateral olfactory bulbectomy on N-methyl-D-aspartate receptor function: autoradiographic and behavioral studies in the rat. Synapse 2001; 42: 95-103.
34. Webster HH, Flores G, Marcotte ER, et al. Olfactory bulbectomy alters NMDA receptor levels in the rat prefrontal cortex. Synapse 2000; 37: 159-62.
35. Oh S, Hoshi K, Ho IK. Role of NMDA receptors in pentobarbital tolerance/dependence. Neurochem Res 1997; 22: 767-74.
36. Short KR, Tabakoff B. Chronic barbiturate treatment increases NMDA receptors but decreases kainate receptors in mouse cortex. Eur J Pharmacol 1993; 230: 111-4.
37. Wieronska JM, Legutko B, Dudys D, Pilc A. Olfactory bulbectomy and amitriptyline treatment influences mGlu receptors expression in the mouse brain hippocampus. Pharmacol Rep 2008; 60: 844-55.
38. Maier SF. Learned helplessness and animal models of depression. Prog Neuropsychopharmacol Biol Psychiatry 1984; 8: 435-46.
39. Almeida RF, Thomazi AP, Godinho GF, et al. Effects of depressive-like behavior of rats on brain glutamate uptake. Neurochem Res 2010; 35: 1164-71.
40. Zink M, Vollmayr B, Gebicke-Haerter PJ, Henn FA. Reduced expression of glutamate transporters vGluT1, EAAT2 and EAAT4 in learned helpless rats, an animal model of depression. Neuropharmacology 2010; 58: 465-73.
41. Ma XC, Jiang D, Jiang WH, et al. Social isolation-induced aggression potentiates anxiety and depressive-like behaviors in male mice subjected to unpredictable chronic mild stress. PLoS One 2011; 6: e20955.
42. Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl) 1997; 134: 319-29.
43. Wieronska JM, Branski P, Szewczyk B, et al. Changes in the expression of metabotropic glutamate receptor 5 (mGluR5) in the rat hippocampus in an animal model of depression. Pol J Pharmacol 2001; 53: 659-62.
44. Toth E, Gersner R, Wilf-Yarkoni A, et al. Age-dependent effects of chronic stress on brain plasticity and depressive behavior. J Neurochem 2008; 107: 522-32.
45. Malkesman O, Weller A. Two different putative genetic animal models of childhood depression--a review. Prog Neurobiol 2009; 88: 153-69.
46. Overstreet DH, Friedman E, Mathe AA, Yadid G. The Flinders Sensitive Line rat: a selectively bred putative animal model of depression. Neurosci Biobehav Rev 2005; 29: 739-59.
47. Ryan B, Musazzi L, Mallei A, et al. Remodelling by early-life stress of NMDA receptor-dependent synaptic plasticity in a geneenvironment rat model of depression. Int J Neuropsychopharmacol 2009; 12: 553-9.
48. Matrisciano F, Caruso A, Orlando R, et al. Defective group-II metaboropic glutamate receptors in the hippocampus of spontaneously depressed rats. Neuropharmacology 2008; 55: 525-31.
49. Elfving B, Plougmann PH, Muller HK, et al. Inverse correlation of brain and blood BDNF levels in a genetic rat model of depression. Int J Neuropsychopharmacol 2010; 13: 563-72.
50. McArthur R, Borsini F. Animal models of depression in drug discovery: a historical perspective. Pharmacol Biochem Behav 2006; 84: 436-52.
51. O'Mahony CM, Bravo JA, Dinan TG, Cryan JF. Comparison of hippocampal metabotropic glutamate receptor 7 (mGlu7) mRNA levels in two animal models of depression. Neurosci Lett 2010; 482: 137-41.
52. Kim JS, Schmid-Burgk W, Claus D, Kornhuber HH. Increased serum glutamate in depressed patients. Arch Psychiatr Nervenkr 1982; 232: 299-304.
53. Altamura CA, Mauri MC, Ferrara A, et al. Plasma and platelet excitatory amino acids in psychiatric disorders. Am J Psychiatry 1993; 150: 1731-3.
54. Mauri MC, Ferrara A, Boscati L, et al. Plasma and platelet amino acid concentrations in patients affected by major depression and under fluvoxamine treatment. Neuropsychobiology 1998; 37: 124-9.
55. Mitani H, Shirayama Y, Yamada T, et al. Correlation between plasma levels of glutamate, alanine and serine with severity of depression. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 1155-8.
56. Maes M, Verkerk R, Vandoolaeghe E, Lin A, Scharpe S. Serum levels of excitatory amino acids, serine, glycine, histidine, threonine, taurine, alanine and arginine in treatment-resistant depression: modulation by treatment with antidepressants and prediction of clinical responsivity. Acta Psychiatr Scand 1998; 97: 302-8.
57. Hashimoto K, Sawa A, Iyo M. Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry 2007; 62: 1310-6.
58. Sanacora G, Gueorguieva R, Epperson CN, et al. Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry 2004; 61: 705-13.
59. Auer DP, Putz B, Kraft E, et al. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry 2000; 47: 305-13.
60. Hasler G, van der Veen JW, Tumonis T, et al. Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry 2007; 64: 193-200.
61. Block W, Traber F, von Widdern O, et al. Proton MR spectroscopy of the hippocampus at 3 T in patients with unipolar major depressive disorder: correlates and predictors of treatment response. Int J Neuropsychopharmacol 2009; 12: 415-22.
62. Valentine GW, Sanacora G. Targeting glial physiology and glutamate cycling in the treatment of depression. Biochem Pharmacol 2009; 78: 431-9.
63. Nudmamud-Thanoi S, Reynolds GP. The NR1 subunit of the glutamate/NMDA receptor in the superior temporal cortex in schizophrenia and affective disorders. Neurosci Lett 2004; 372: 173-7.
64. Beneyto M, Kristiansen LV, Oni-Orisan A, McCullumsmith RE, Meador-Woodruff JH. Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology 2007; 32: 1888-902.
65. Feyissa AM, Chandran A, Stockmeier CA, Karolewicz B. Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 70-5.
66. Feyissa AM, Woolverton WL, Miguel-Hidalgo JJ, et al. Elevated level of metabotropic glutamate receptor 2/3 in the prefrontal cortex in major depression. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 279-83.
67. Karolewicz B, Szebeni K, Gilmore T, et al. Elevated levels of NR2A and PSD-95 in the lateral amygdala in depression. Int J Neuropsychopharmacol 2009; 12: 143-53.
68. Deschwanden A, Karolewicz B, Feyissa AM, et al. Reduced metabotropic glutamate receptor 5 density in major depression determined by [11C]ABP688 PET and postmortem study. Am J Psychiatry 2011; 168: 727-34.
69. Domino EF. Taming the ketamine tiger. 1965. Anesthesiology 2010; 113: 678-84.
70. Machado-Vieira R, Salvadore G, Diazgranados N, Zarate CA Jr. Ketamine and the next generation of antidepressants with a rapid onset of action. Pharmacol Ther 2009; 123: 143-50.
71. Zarate C Jr, Machado-Vieira R, Henter I, Ibrahim L, Diazgranados N, Salvadore G. Glutamatergic modulators: the future of treating mood disorders? Harv Rev Psychiatry 2010; 18: 293-303.
72. da Silva FC, do Carmo de Oliveira Cito M, da Silva MI, et al. Behavioral alterations and pro-oxidant effect of a single ketamine administration to mice. Brain Res Bull 2010; 83: 9-15.
73. Engin E, Treit D, Dickson CT. Anxiolytic-and antidepressant-like properties of ketamine in behavioral and neurophysiological animal models. Neuroscience 2009; 161: 359-69.
74. Garcia LS, Comim CM, Valvassori SS, et al. Chronic administration of ketamine elicits antidepressant-like effects in rats without affecting hippocampal brain-derived neurotrophic factor protein levels. Basic Clin Pharmacol Toxicol 2008; 103: 502-6.
75. Garcia LS, Comim CM, Valvassori SS, et al. Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 140-4.
76. Li N, Lee B, Liu RJ, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 2010; 329: 959-64.
77. Maeng S, Zarate CA Jr, Du J, et al. Cellular mechanisms underlying the antidepressant effects of ketamine: role of_-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry 2008; 63: 349-52.
78. Rosa AO, Lin J, Calixto JB, Santos AR, Rodrigues AL. Involvement of NMDA receptors and L-arginine-nitric oxide pathway in the antidepressant-like effects of zinc in mice. Behav Brain Res 2003; 144: 87-93.
79. Yilmaz A, Schulz D, Aksoy A, Canbeyli R. Prolonged effect of an anesthetic dose of ketamine on behavioral despair. Pharmacol Biochem Behav 2002; 71: 341-4.
80. Kos T, Popik P, Pietraszek M, et al. Effect of 5-HT3 receptor antagonist MDL 72222 on behaviors induced by ketamine in rats and mice. Eur Neuropsychopharmacol 2006; 16: 297-310.
81. Chaturvedi HK, Chandra D, Bapna JS. Interaction between Nmethyl-D-aspartate receptor antagonists and imipramine in shockinduced depression. Indian J Exp Biol 1999; 37: 952-8.
82. Garcia LS, Comim CM, Valvassori SS, Reus, et al. Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 450-5.
83. Ma XC, Dang YH, Jia M, et al. Long-lasting antidepressant action of ketamine, but not glycogen synthase kinase-3 inhibitor SB216763, in the chronic mild stress model of mice. PLoS One 2013; 8: e56053.
84. Li N, Liu RJ, Dwyer JM, et al. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry 2011; 69: 754-61.
85. Hashimoto K. Role of mTOR signaling pathway in the rapid antidepressant action of ketamine. Expert Rev Neurother 2011; 11: 33-6.
86. Cryan JF, O'Leary OF. Neuroscience. A glutamate pathway to faster-acting antidepressants? Science 2010; 329: 913-4.
87. Koike H, Iijima M, Chaki S. Involvement of the mammalian target of rapamycin signaling in the antidepressant-like effect of group II metabotropic glutamate receptor antagonists. Neuropharmacology 2011; 61: 1419-23.
88. Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 2000; 47: 351-4.
89. Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006; 63: 856-64.
90. Diazgranados N, Ibrahim L, Brutsche NE, et al. A randomized addon trial of an N-methyl-D-aspartate antagonist in treatmentresistant bipolar depression. Arch Gen Psychiatry 2010; 67: 793-802.
91. Zarate CA Jr, Brutsche NE, Ibrahim L, et al. Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry 2012; 71: 939-46.
92. Krystal JH. N-methyl-D-aspartate glutamate antagonists and the promise of rapid-acting antidepressants. Arch Gen Psychiatry 2010; 67: 1110-11.
93. Aan Het Rot M, Zarate CA Jr, Charney DS, Mathew SJ. Ketamine for depression: Where do we go from here? Biol Psychiatry 2012; 72: 537-47.
94. Machado-Vieira R, Salvadore G, Luckenbaugh DA, Manji HK, Zarate CA Jr. Rapid onset of antidepressant action: a new paradigm in the research and treatment of major depressive disorder. J Clin Psychiatry 2008; 69: 946-58.
95. Liebrenz M, Stohler R, Borgeat A. Repeated intravenous ketamine therapy in a patient with treatment-resistant major depression. World J Biol Psychiatry 2009; 10: 640-3.
96. Dillon P, Copeland J, Jansen K. Patterns of use and harms associated with non-medical ketamine use. Drug Alcohol Depend 2003; 69: 23-8.
97. Sinner B, Graf BM. Ketamine. Handb Exp Pharmacol 2008; 182: 313-33.
98. Paul R, Schaaff N, Padberg F, Moller HJ, Frodl T. Comparison of racemic ketamine and S-ketamine in treatment-resistant major depression: report of two cases. World J Biol Psychiatry 2009; 10: 241-4.
99. Johnson JW, Kotermanski SE. Mechanism of action of memantine. Curr Opin Pharmacol 2006; 6: 61-7.
100. Mony L, Kew JN, Gunthorpe MJ, Paoletti P. Allosteric modulators of NR2B-containing NMDA receptors: molecular mechanisms and therapeutic potential. Br J Pharmacol 2009; 157: 1301-17.
101. Reus GZ, Stringari RB, Kirsch TR, et al. Neurochemical and behavioural effects of acute and chronic memantine administration in rats: Further support for NMDA as a new pharmacological target for the treatment of depression? Brain Res Bull 2010; 81: 585-9.
102. Rogoz Z, Skuza G, Maj J, Danysz W. Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats. Neuropharmacology 2002; 42: 1024-30.
103. Tokita K, Fujita Y, Yamaji T, Hashimoto K. Depressive-like behavior in adrenocorticotropic hormone-treated rats blocked by memantine. Pharmacol Biochem Behav 2012; 102: 329-34.
104. Thomas SJ, Grossberg GT. Memantine: a review of studies into its safety and efficacy in treating Alzheimer's disease and other dementias. Clin Interv Aging 2009; 4: 367-77.
105. Parsons CG, Stoffler A, Danysz W. Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system--too little activation is bad, too much is even worse. Neuropharmacology 2007; 53: 699-723.
106. Zarate CA Jr, Singh JB, Quiroz JA, et al. A double-blind, placebocontrolled study of memantine in the treatment of major depression. Am J Psychiatry 2006; 163: 153-5.
107. Ferguson JM, Shingleton RN. An open-label, flexible-dose study of memantine in major depressive disorder. Clin Neuropharmacol 2007; 30: 136-44.
108. Muhonen LH, Lonnqvist J, Juva K, Alho H. Double-blind, randomized comparison of memantine and escitalopram for the treatment of major depressive disorder comorbid with alcohol dependence. J Clin Psychiatry 2008; 69: 392-9
109. Sanacora G, Smith MA, Pathak S, et al. Lanicemine: a lowtrapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects. Mol Psychiatry 2013 Oct 15. doi: 10.1038/mp.2013.130. [Epub ahead of print]
110. Zarate CA, Mathews D, Ibrahim L, et al. A randomized trial of a low trapping non-selective N-methyl-D-aspartate (NMDA) channel blocker in major depression. Biol Psychiatry 2013; 74: 257-64.
111. Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 1991; 148: 1301-8.
112. 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.
113. Krystal JH, Perry EB Jr, Gueorguieva R, et al. Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine: implications for glutamatergic and dopaminergic model psychoses and cognitive function. Arch Gen Psychiatry 2005; 62: 985-94.
114. Moryl E, Danysz W, Quack G. Potential antidepressive properties of amantadine, memantine and bifemelane. Pharmacol Toxicol 1993; 72: 394-7.
115. Kemp JA, McKernan RM. NMDA receptor pathways as drug targets. Nat Neurosci 2002; 5 (Suppl): 1039-42.
116. Preskorn SH, Baker B, Kolluri S, et al. An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. J Clin Psychopharmacol 2008; 28: 631-7.
117. Hashimoto K, London ED. Further characterization of [3H]ifenprodil binding to sigma receptors in rat brain. Eur J Pharmacol 1993; 236: 159-63.
118. Coughenour LA, Barr BM. Use of trifluoroperazine isolates a [3H]ifenprodil binding site in rat brain membranes with the pharmacology of the voltage-independent idenprodil site on N-methyl-D-aspartate receptors containing NR2B subunits. J Pharmacol Exp Ther 2001; 296: 150-9.
119. Ishima T, Hashimoto K. Potentiation of nerve groth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors. PLoS One 2012; 7: e37989.
120. Hashimoto K. Sigma-1 receptor chaperone and brain-derived neurotrophic factor: emerging links between cardiovascular disease and depression. Prog Neurobiol 2013; 100: 15-29.
121. Hashimoto K. Comments to “An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder”. J Clin Psychopharmacol 2009; 29: 411-2.
122. Addy C, Assaid C, Hreniuk D, et al. Single-dose administration of MK-0657, an NR2B-selective NMDA antagonist, does not result in clinically meaningful improvement in motor function in patients with moderate Parkinson's disease. J Clin Pharmacol 2009; 49: 856-64.
123. Ibrahim L, Diaz Granados N, Jolkovsky L, et al. A Randomized, placebo-controlled, crossover pilot trial of the oral selective NR2B antagonist MK-0657 in patients with treatment-resistant major depressive disorder. J Clin Psychopharmacol 2012; 32: 551-7.
124. Moskal JR, Kuo AG, Weiss C, et al. GLYX-13: a monoclonal antibody-derived peptide that acts as an N-methyl-D-aspartate receptor modulator. Neuropharmacology 2005; 49: 1077-87.
125. Moskal JR, Burgdorf J, Kroes RA, Brudzynski SM, Panksepp J. A novel NMDA receptor glycine-site partial agonist, GLYX-13, has therapeutic potential for the treatment of autism. Neurosci Biobehav Rev 2011; 35: 1982-8.
126. Burgdorf JS, Zhang XL, Nicholson KL, et al. GLYX-13, an NMDA receptor glycine-site functional partial agonist, induces antidepressant-like effects without ketamine-like side effects. Neuropsychopharmacology 2013; 38: 729-42.
127. Hashimoto K, Malchow B, Falkai P, Schmitt A Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders. Eur Arch Psychiatry Clin Neurosci 2013; 263: 367-77.
128. Hashimoto K. Therapeutic implications for NMDA receptors in mood disorders. Expert Rev Neurother 2013; 13: 735-7.
129. U.S. National Institutes of Health, ClinicalTrials Web Site [Homepage on the Internet]. Safety and pharmacokonetics of NRX-1074 in healthy volunteers. http://clinicaltrials.gov/ct2/show/NCT01856556.
130. Heresco-Levy U, Gelfin G, Bloch B, Levin R, Edelman S, Javitt DC, Kremer I. A randomized add-on trial of high-dose Dcycloserine for treatment-resistant depression. Int J Neuropsychopharmacol 2013; 16: 501-6.
131. Hashimoto K. Glycine transporter-1 inhibitors as novel therapeutic drugs for schizophrenia. Cent Nerv Syst Agents Med Chem 2007; 7: 177-82.
132. Hashimoto K. Glycine transportor-1: a potential therapeutic target for schizophrenia. Curr Pharm Des 2011; 17: 112-20.
133. Javitt DC. Glycine transport inhibitors in the treatment of schizophrenia. Handb Exp Pharmacol 2012; 213: 367-99.
134. Tsai GE, Lin PY. Strategies to enhance N-methyl-D-aspartate receptor-mediated neurotransmission in schizophrenia. A critical review and meta-analysis. Curr Pham Des 2010; 16: 522-37.
135. Huang CC, Wei IH, Huang CL, et al. Inhibition of glycine transpiorter-1 as a novel mechanism for the treatment of depression. Biol Psychiatry 2013; 74: 734-41.
136. Pinard E, Alanine A, Alberati D, et al. Selective 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.
137. Alberati D, Moreau JL, Lengyel J, et al. Glycine reuptake inhibitor RG1678: a pharmacologic characterization of an investigational agent for the treatment of schizophrenia. Neuropharmacology 2012; 62: 1152-61.