Targeting glutamate synapses in schizophrenia

Trends in Molecular Medicine

Volumn 17, Issue 12, 2011, Pages 689-698

  Field, Julie R ^a   Walker, Adam G ^a   Conn, P Jeffrey ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINO 2 OXABICYCLO[3.1.0]HEXANE 4,6 DICARBOXYLIC ACID; 4 AMINO 2 THIABICYCLO[3.1.0]HEXANE 4,6 DICARBOXYLIC ACID 2,2 DIOXIDE; 4 AMINOBUTYRIC ACID RECEPTOR; ALPHA AMINO 3 HYDROXY 5 METHYL 4 ISOXAZOLEPROPIONIC ACID; AMPA RECEPTOR; CHOLINESTERASE INHIBITOR; CLOZAPINE; DIZOCILPINE; EGLUMETAD; GLUTAMATE RECEPTOR; GLUTAMATE RECEPTOR 2; GLUTAMATE RECEPTOR 3; GLUTAMATE RECEPTOR 5; GLUTAMIC ACID; GLYCINE TRANSPORTER 1; LY 2033298; MUSCARINIC RECEPTOR; N METHYL DEXTRO ASPARTIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NEUROLEPTIC AGENT; NEUROTRANSMITTER; POMAGLUMETAD METHIONIL; RG 1678; SARCOSINE; SEROTONIN 2 RECEPTOR; SSR 103800; SSR 504743; UNCLASSIFIED DRUG; UNINDEXED DRUG; VU 0010010; XANOMELINE;

AMYGDALOID NUCLEUS; CENTRAL NERVOUS SYSTEM; DOPAMINERGIC ACTIVITY; DRUG ACTIVITY; DRUG EFFICACY; DRUG TARGETING; GABAERGIC SYSTEM; HIPPOCAMPUS; HUMAN; INTERNEURON; MONOAMINERGIC SYSTEM; NERVE CELL; NONHUMAN; POSITIVE SYNDROME; PREFRONTAL CORTEX; REVIEW; SCHIZOPHRENIA; SIGNAL TRANSDUCTION; UNSPECIFIED SIDE EFFECT; VISUAL CORTEX;

ANIMALS; ANTIPSYCHOTIC AGENTS; EXCITATORY AMINO ACID AGONISTS; GLYCINE PLASMA MEMBRANE TRANSPORT PROTEINS; HUMANS; LIGANDS; MICE; MICE, KNOCKOUT; MUSCARINIC AGONISTS; RATS; RECEPTORS, METABOTROPIC GLUTAMATE; RECEPTORS, MUSCARINIC; RECEPTORS, N-METHYL-D-ASPARTATE; SCHIZOPHRENIA; SYNAPSES; SYNAPTIC TRANSMISSION;

EID: 84855927044     PISSN: 14714914     EISSN: 1471499X     Source Type: Journal    
DOI: 10.1016/j.molmed.2011.08.004     Document Type: Review

References (112)

1. Swerdlow N.R. Integrative circuit models and their implications for the pathophysiologies and treatments of the schizophrenias. Curr. Top. Behav. Neurosci. 2011, 4:555-583.
2. Lewis D.A., Sweet R.A. Schizophrenia from a neural circuitry perspective: advancing toward rational pharmacological therapies. J. Clin. Invest. 2009, 119:706-716.
3. Cronenwett W.J., Csernansky J. Thalamic pathology in schizophrenia. Curr. Top. Behav. Neurosci. 2011, 4:509-528.
4. Volk D.W., Lewis D.A. Prefrontal cortical circuits in schizophrenia. Curr. Top. Behav. Neurosci. 2011, 4:485-508.
5. Benes F.M. Neural circuitry models of schizophrenia: is it dopamine, GABA, glutamate, or something else?. Biol. Psychiatry 2009, 65:1003-1005.
6. Simpson E.H., et al. A possible role for the striatum in the pathogenesis of the cognitive symptoms of schizophrenia. Neuron 2010, 65:585-596.
7. Dorph-Petersen K.A., et al. Pyramidal neuron number in layer 3 of primary auditory cortex of subjects with schizophrenia. Brain Res. 2009, 1285:42-57.
8. Dorph-Petersen K.A., et al. Primary visual cortex volume and total neuron number are reduced in schizophrenia. J. Comp. Neurol. 2007, 501:290-301.
9. Smiley J.F., et al. Hemispheric comparisons of neuron density in the planum temporale of schizophrenia and nonpsychiatric brains. Psychiatry Res. 2011, 192:1-11.
10. Ellison-Wright I., Bullmore E. Anatomy of bipolar disorder and schizophrenia: a meta-analysis. Schizophr. Res. 2010, 117:1-12.
11. Lisman J.E., et al. Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci. 2008, 31:234-242.
12. Featherstone R.E., et al. The amphetamine-induced sensitized state as a model of schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry 2007, 31:1556-1571.
13. Javitt D.C., Zukin S.R. Recent advances in the phencyclidine model of schizophrenia. Am. J. Psychiatry 1991, 148:1301-1308.
14. Krystal J.H., 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.
15. Konradi C., Heckers S. Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment. Pharmacol. Ther. 2003, 97:153-179.
16. Coyle J.T. Glutamate and schizophrenia: beyond the dopamine hypothesis. Cell. Mol. Neurobiol. 2006, 26:365-384.
17. Javitt D.C. Glutamatergic theories of schizophrenia. Isr. J. Psychiatry Relat. Sci. 2010, 47:4-16.
18. Olney J.W., et al. NMDA receptor hypofunction model of schizophrenia. J. Psychiatry Res. 1999, 33:523-533.
19. Moghaddam B., Adams B.W. Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science 1998, 281:1349-1352.
20. Lynch D.R., Guttmann R.P. Excitotoxicity: perspectives based on N-methyl-D-aspartate receptor subtypes. J. Pharmacol. Exp. Ther. 2002, 300:717-723.
21. Dingledine R., et al. The glutamate receptor ion channels. Pharmacol. Rev. 1999, 51:7-61.
22. Niswender C.M., Conn P.J. Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu. Rev. Pharmacol. Toxicol. 2010, 50:295-322.
23. Conn P.J., et al. Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nat. Rev. Drug Discov. 2009, 8:41-54.
24. Conn P.J., et al. Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia. Trends Pharmacol. Sci. 2009, 30:25-31.
25. Brody S.A., et al. Assessment of a prepulse inhibition deficit in a mutant mouse lacking mGlu5 receptors. Mol. Psychiatry 2004, 9:35-41.
26. Kinney G.G., et al. Metabotropic glutamate subtype 5 receptors modulate locomotor activity and sensorimotor gating in rodents. J. Pharmacol. Exp. Ther. 2003, 306:116-123.
27. Campbell U.C., et al. The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) potentiates PCP-induced cognitive deficits in rats. Psychopharmacology (Berl) 2004, 175:310-318.
28. Ayala J.E., et al. mGluR5 positive allosteric modulators facilitate both hippocampal LTP and LTD and enhance spatial learning. Neuropsychopharmacology 2009, 34:2057-2071.
29. Wong R.K., et al. Group I mGluR-induced epileptogenesis: distinct and overlapping roles of mGluR1 and mGluR5 and implications for antiepileptic drug design. Epilepsy Curr. 2005, 5:63-68.
30. O'Brien J.A., et al. A family of highly selective allosteric modulators of the metabotropic glutamate receptor subtype 5. Mol. Pharmacol. 2003, 64:731-740.
31. O'Brien J.A., et al. A novel selective allosteric modulator potentiates the activity of native metabotropic glutamate receptor subtype 5 in rat forebrain. J. Pharmacol. Exp. Ther. 2004, 309:568-577.
32. Kinney G.G., et al. A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and antipsychotic-like effects in rat behavioral models. J. Pharmacol. Exp. Ther. 2005, 313:199-206.
33. Uslaner J.M., et al. Dose-dependent effect of CDPPB, the mGluR5 positive allosteric modulator, on recognition memory is associated with GluR1 and CREB phosphorylation in the prefrontal cortex and hippocampus. Neuropharmacology 2009, 57:531-538.
34. Lecourtier L., et al. Positive allosteric modulation of metabotropic glutamate 5 (mGlu5) receptors reverses N-methyl-D-aspartate antagonist-induced alteration of neuronal firing in prefrontal cortex. Biol. Psychiatry 2007, 62:739-746.
35. Darrah J.M., et al. Interaction of N-methyl-D-aspartate and group 5 metabotropic glutamate receptors on behavioral flexibility using a novel operant set-shift paradigm. Behav. Pharmacol. 2008, 19:225-234.
36. Stefani M.R., Moghaddam B. Activation of type 5 metabotropic glutamate receptors attenuates deficits in cognitive flexibility induced by NMDA receptor blockade. Eur. J. Pharmacol. 2010, 639:26-32.
37. Liu F., et al. ADX47273 [S-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]-oxadiazol-5-yl]-piper idin-1-yl}-methanone]: a novel metabotropic glutamate receptor 5-selective positive allosteric modulator with preclinical antipsychotic-like and procognitive activities. J. Pharmacol. Exp. Ther. 2008, 327:827-839.
38. Rodriguez A.L., et al. Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity. Mol. Pharmacol. 2010, 78:1105-1123.
39. Rodriguez A.L., et al. Discovery and SAR of novel mGluR5 non-competitive antagonists not based on an MPEP chemotype. Bioorg. Med. Chem. Lett. 2009, 19:3209-3213.
40. Spear N., et al. Preclinical profile of a novel metabotropic glutamate receptor 5 positive allosteric modulator. Eur. J. Pharmacol. 2011, 659:146-154.
41. Marek G.J. Metabotropic glutamate 2/3 (mGlu2/3) receptors, schizophrenia and cognition. Eur. J. Pharmacol. 2010, 639:81-90.
42. Cartmell J., et al. The metabotropic glutamate 2/3 receptor agonists LY354740 and LY379268 selectively attenuate phencyclidine versus d-amphetamine motor behaviors in rats. J. Pharmacol. Exp. Ther. 1999, 291:161-170.
43. Homayoun H., et al. Activation of metabotropic glutamate 2/3 receptors reverses the effects of NMDA receptor hypofunction on prefrontal cortex unit activity in awake rats. J. Neurophysiol. 2005, 93:1989-2001.
44. Pehrson A.L., Moghaddam B. Impact of metabotropic glutamate 2/3 receptor stimulation on activated dopamine release and locomotion. Psychopharmacology (Berl) 2010, 211:443-455.
45. Higgins G.A., et al. Pharmacological manipulation of mGlu2 receptors influences cognitive performance in the rodent. Neuropharmacology 2004, 46:907-917.
46. Schlumberger C., et al. Effects of a metabotropic glutamate receptor group II agonist LY354740 in animal models of positive schizophrenia symptoms and cognition. Behav. Pharmacol. 2009, 20:56-66.
47. Krystal J.H., et al. Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects. Psychopharmacology (Berl) 2005, 179:303-309.
48. Patil S.T., et al. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized phase 2 clinical trial. Nat. Med. 2007, 13:1102-1107.
49. Kinon B.J., et al. Placebo response in clinical trials with schizophrenia patients. Curr. Opin. Psychiatry 2011, 24:107-113.
50. Ghose S., et al. Localization of NAAG-related gene expression deficits to the anterior hippocampus in schizophrenia. Schizophr. Res. 2009, 111:131-137.
51. Ghose S., et al. Differential expression of metabotropic glutamate receptors 2 and 3 in schizophrenia: a mechanism for antipsychotic drug action?. Am. J. Psychiatry 2009, 166:812-820.
52. Fell M.J., et al. Evidence for the role of metabotropic glutamate (mGlu)2 not mGlu3 receptors in the preclinical antipsychotic pharmacology of the mGlu2/3 receptor agonist (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY404039). J. Pharmacol. Exp. Ther. 2008, 326:209-217.
53. Woolley M.L., et al. The mGlu2 but not the mGlu3 receptor mediates the actions of the mGluR2/3 agonist, LY379268, in mouse models predictive of antipsychotic activity. Psychopharmacology (Berl) 2008, 196:431-440.
54. Gonzalez-Maeso J., et al. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 2008, 452:93-97.
55. Molinaro G., et al. Activation of mGlu2/3 metabotropic glutamate receptors negatively regulates the stimulation of inositol phospholipid hydrolysis mediated by 5-hydroxytryptamine2A serotonin receptors in the frontal cortex of living mice. Mol. Pharmacol. 2009, 76:379-387.
56. Liu W., et al. Pharmacogenetic analysis of the mGlu2/3 agonist LY2140023 monohydrate in the treatment of schizophrenia. Pharmacogenomics J 2010, 10.1038/tpj.2010.90.
57. Galici R., et al. A selective allosteric potentiator of metabotropic glutamate (mGlu) 2 receptors has effects similar to an orthosteric mGlu2/3 receptor agonist in mouse models predictive of antipsychotic activity. J. Pharmacol. Exp. Ther. 2005, 315:1181-1187.
58. Bonnefous C., et al. Biphenyl-indanones: allosteric potentiators of the metabotropic glutamate subtype 2 receptor. Bioorg. Med. Chem. Lett. 2005, 15:4354-4358.
59. Johnson M.P., et al. Metabotropic glutamate 2 receptor potentiators: receptor modulation, frequency-dependent synaptic activity, and efficacy in preclinical anxiety and psychosis model(s). Psychopharmacology (Berl) 2005, 179:271-283.
60. Benneyworth M.A., et al. A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis. Mol. Pharmacol. 2007, 72:477-484.
61. Hackler E.A., et al. Selective potentiation of the metabotropic glutamate receptor subtype 2 blocks phencyclidine-induced hyperlocomotion and brain activation. Neuroscience 2010, 168:209-218.
62. Langmead C.J., et al. Muscarinic acetylcholine receptors as CNS drug targets. Pharmacol. Ther. 2008, 117:232-243.
63. Wess J., et al. Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development. Nat. Rev. Drug Discov. 2007, 6:721-733.
64. Marino M.J., et al. Activation of the genetically defined m1 muscarinic receptor potentiates N-methyl-D-aspartate (NMDA) receptor currents in hippocampal pyramidal cells. Proc. Natl. Acad. Sci. U.S.A. 1998, 95:11465-11470.
65. Bodick N.C., et al. Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch. Neurol. 1997, 54:465-473.
66. Shekhar A., et al. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am. J. Psychiatry 2008, 165:1033-1039.
67. Bymaster F.E., et al. Xanomeline: a selective muscarinic agonist for the treatment of Alzheimer's disease. Drug Dev. Res. 1997, 40:158-170.
68. Sramek J.J., et al. The safety and tolerance of xanomeline tartrate in patients with Alzheimer's disease. J. Clin. Pharmacol. 1995, 35:800-806.
69. Conn P.J., et al. Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders. Trends Pharmacol. Sci. 2009, 30:148-155.
70. Sur C., et al. N-Desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates N-methyl-D-aspartate receptor activity. Proc. Natl. Acad. Sci. U.S.A. 2003, 100:13674-13679.
71. Davies M.A., et al. The highly efficacious actions of N-desmethylclozapine at muscarinic receptors are unique and not a common property of either typical or atypical antipsychotic drugs: is M1 agonism a pre-requisite for mimicking clozapine's actions?. Psychopharmacology (Berl) 2005, 178:451-460.
72. Weiner D.M., et al. The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine. Psychopharmacology (Berl) 2004, 177:207-216.
73. Mendoza M.C., Lindenmayer J.P. N-Desmethylclozapine: is there evidence for its antipsychotic potential?. Clin. Neuropharmacol. 2009, 32:154-157.
74. Bradley S.R., et al. AC-260584, an orally bioavailable M(1) muscarinic receptor allosteric agonist, improves cognitive performance in an animal model. Neuropharmacology 2009, 58:365-373.
75. Jones C.K., et al. Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in rats. J. Neurosci. 2008, 28:10422-10433.
76. Langmead C.J., et al. Characterization of a CNS penetrant, selective M1 muscarinic receptor agonist, 77-LH-28-1. Br. J. Pharmacol. 2008, 154:1104-1115.
77. Lebois E.P., et al. Discovery and characterization of novel subtype-selective allosteric agonists for the investigation of M1 receptor function in the central nervous system. ACS Chem. Neurosci. 2010, 1:104-121.
78. Gregory K.J., et al. Allosteric modulation of muscarinic acetylcholine receptors. Curr. Neuropharmacol. 2007, 5:157-167.
79. Valant C., et al. A novel mechanism of G protein-coupled receptor functional selectivity. Muscarinic partial agonist McN-A-343 as a bitopic orthosteric/allosteric ligand. J. Biol. Chem. 2008, 283:29312-29321.
80. Ma L., et al. Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:15950-15955.
81. Shirey J.K., et al. A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning. J. Neurosci. 2009, 29:14271-14286.
82. Dencker D., et al. Involvement of a subpopulation of neuronal M4 muscarinic acetylcholine receptors in the antipsychotic-like effects of the M1/M4 preferring muscarinic receptor agonist xanomeline. J. Neurosci. 2011, 31:5905-5908.
83. Lazareno S., et al. Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor subtype selectivity via cooperativity rather than affinity. Mol. Pharmacol. 2004, 65:257-266.
84. Chan W.Y., et al. Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:10978-10983.
85. Shirey J.K., et al. An allosteric potentiator of M4 mAChR modulates hippocampal synaptic transmission. Nat. Chem. Biol. 2008, 4:42-50.
86. Brady A.E., et al. Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats. J. Pharmacol. Exp. Ther. 2008, 327:941-953.
87. Bridges T.M., et al. Discovery and development of a highly selective M1 positive allosteric modulator (PAM). Probe Reports from the NIH Molecular Libraries Program 2010, National Center for Biotechnology Information.
88. Bridges T.M., et al. Discovery and development of a second highly selective M1 positive allosteric modulator (PAM). Probe Reports from the NIH Molecular Libraries Program 2010, National Center for Biotechnology Information.
89. Lewis L.M., et al. Discovery of a highly selective in vitro and in vivo M4 positive allosteric modulator (PAM). Probe Reports from the NIH Molecular Libraries Program 2010, National Center for Biotechnology Information.
90. Lin C.H., et al. Glutamate signaling in the pathophysiology and therapy of schizophrenia. Pharmacol. Biochem. Behav. 2011, 10.1016/j.pbb.2011.03.023.
91. Mohler H., et al. Glycine transporter 1 as a potential therapeutic target for schizophrenia-related symptoms: evidence from genetically modified mouse models and pharmacological inhibition. Biochem. Pharmacol. 2011, 81:1065-1077.
92. Raiteri L., Raiteri M. Functional 'glial' GLYT1 glycine transporters expressed in neurons. J. Neurochem. 2010, 114:647-653.
93. Kinney G.G., 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, 23:7586-7591.
94. Perry K.W., et al. Neurochemical and behavioral profiling of the selective GlyT1 inhibitors ALX5407 and LY2365109 indicate a preferential action in caudal vs. cortical brain areas. Neuropharmacology 2008, 55:743-754.
95. Yang C.R., Svensson K.A. Allosteric modulation of NMDA receptor via elevation of brain glycine and D-serine: the therapeutic potentials for schizophrenia. Pharmacol. Ther. 2008, 120:317-332.
96. Kopec K., et al. Glycine transporter (GlyT1) inhibitors with reduced residence time increase prepulse inhibition without inducing hyperlocomotion in DBA/2 mice. Biochem. Pharmacol. 2010, 80:1407-1417.
97. Lindsley C.W., et al. Progress towards validating the NMDA receptor hypofunction hypothesis of schizophrenia. Curr. Top. Med. Chem. 2006, 6:771-785.
98. Lindsley C., 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. ChemMedChem 2006, 1:807-811.
99. Black M.D., 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, 202:385-396.
100. Boulay D., et al. The glycine transporter-1 inhibitor SSR103800 displays a selective and specific antipsychotic-like profile in normal and transgenic mice. Neuropsychopharmacology 2010, 35:416-427.
101. Pinard E., et al. Discovery of benzoylisoindolines as a novel class of potent, selective and orally active GlyT1 inhibitors. Bioorg. Med. Chem. Lett. 2010, 20:6960-6965.
102. Schlumberger C., et al. Comparison of the mGlu(5) receptor positive allosteric modulator ADX47273 and the mGlu(2/3) receptor agonist LY354740 in tests for antipsychotic-like activity. Eur. J. Pharmacol. 2009, 623:73-83.
103. Digby G.J., et al. Allosteric activators of muscarinic receptors as novel approaches for treatment of CNS disorders. Mol. Biosyst. 2010, 6:1345-1354.
104. Chen Y., et al. Interaction of novel positive allosteric modulators of metabotropic glutamate receptor 5 with the negative allosteric antagonist site is required for potentiation of receptor responses. Mol. Pharmacol. 2007, 71:1389-1398.
105. Epping-Jordan M.P., et al. In vivo characterization of mGluR5 positive allosteric modulators as novel treatments for schizophrenia and cognitive dysfunction. Neuropharmacology 2005, 49(Suppl. 1):243.
106. Rorick-Kehn L.M., et al. Pharmacological and pharmacokinetic properties of a structurally novel, potent, and selective metabotropic glutamate 2/3 receptor agonist: in vitro characterization of agonist (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid (LY404039). J. Pharmacol. Exp. Ther. 2007, 321:308-317.
107. Rorick-Kehn L.M., et al. In vivo pharmacological characterization of the structurally novel, potent, selective mGlu2/3 receptor agonist LY404039 in animal models of psychiatric disorders. Psychopharmacology (Berl) 2007, 193:121-136.
108. Johnson M.P., et al. Discovery of allosteric potentiators for the metabotropic glutamate 2 receptor: synthesis and subtype selectivity of N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2- trifluoroethylsulfonyl)pyrid-3-ylmethylamine. J. Med. Chem. 2003, 46:3189-3192.
109. Spalding T.A., et al. Discovery of an ectopic activation site on the M(1) muscarinic receptor. Mol. Pharmacol. 2002, 61:1297-1302.
110. Li Z., et al. AC260584 (4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one), a selective muscarinic M1 receptor agonist, increases acetylcholine and dopamine release in rat medial prefrontal cortex and hippocampus. Eur. J. Pharmacol. 2007, 572:129-137.
111. Marlo J.E., et al. Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity. Mol. Pharmacol. 2009, 75:577-588.
112. Singer P., et al. The glycine transporter 1 inhibitor SSR504734 enhances working memory performance in a continuous delayed alternation task in C57BL/6 mice. Psychopharmacology (Berl) 2009, 202:371-384.