Recent developments in metabotropic glutamate receptors as novel drug targets

Drugs of the Future

Volumn 35, Issue 4, 2010, Pages 307-324

  O'Neill, Michael J ^a   Fell, M J ^a   Svensson, K A ^a   Witkin, J M ^a   Mitchell, S N ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 2 (2 CARBOXYCYCLOPROPYL) 3 (XANTHEN 9 YL)PROPIONIC ACID; 2 AMINO 3 (3,4 DICHLOROBENZYLOXY) 6 FLUOROBICYCLO[3.1.0]HEXANE 2,6 DICARBOXYLIC ACID; 2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; 3 [(2 METHYL 4 THIAZOLYL)ETHYNYL]PYRIDINE; 4 [1 (2 FLUOROPYRIDIN 3 YL) 5 METHYL 1H 1,2,3 TRIAZOL 4 YL] N ISOPROPYL N METHYL 3,6 DIHYDROPYRIDINE 1(2H) CARBOXAMIDE; 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; A 841720; ADX 47273; AFQ 056; AMN 082; EGLUMETAD; IONOTROPIC RECEPTOR; JNJ 16259685; JNJ 16567083; LY 456236; LY 487379; METABOTROPIC RECEPTOR; METABOTROPIC RECEPTOR 1; METABOTROPIC RECEPTOR 2; METABOTROPIC RECEPTOR 3; METABOTROPIC RECEPTOR 4; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR 6; METABOTROPIC RECEPTOR 7; METABOTROPIC RECEPTOR 8; METABOTROPIC RECEPTOR AGONIST; METABOTROPIC RECEPTOR ANTAGONIST; PHOSPHATIDYLINOSITOL; RECEPTOR SUBTYPE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VU 0155041;

ALLODYNIA; ALLOSTERISM; ANXIETY; ANXIETY DISORDER; BIOLOGICAL ACTIVITY; DEPRESSION; DRUG MECHANISM; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; DYSKINESIA; HUMAN; HYPERALGESIA; MIGRAINE; NEUROMODULATION; NONHUMAN; PAIN; PARKINSON DISEASE; POSTOPERATIVE PAIN; REVIEW; SCHIZOPHRENIA; SECOND MESSENGER; SEQUENCE HOMOLOGY; SYNAPTIC TRANSMISSION;

EID: 77954571475     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.2010.035.04.1487693     Document Type: Review

References (194)

1. O'Neill, M.J., Lees, K.R. Ionotropic glutamate receptors as therapeutic targets. In: Therapeutic Potential of Ionotropic Glutamate Receptor Antagonists and Modulators, Chapter 13, Stroke. W. Danysz, D. Lodge, C.G. Parsons (Eds.). F.P. Graham Publishing Co., 2002, 403-47.
2. O'Neill, M.J., McCulloch, J., Lodge, D. Stroke: Mechanisms of excitotoxicity and approaches for therapy. In: Handbook of Contemporary Neuropharmacology. D.R. Sibley, I. Hannin, M. Kuhar, P. Skolnick (Eds.). John Wiley and Sons: New York, 2007.
3. Bowie, D. Ionotropic glutamate receptors & CNS disorders. CNS Neurol Disord Drug Targets 2008, 7(2): 129-43.
4. Paul, I.A., Skolnick, P. Glutamate and depression: Clinical and preclinical studies. Ann N Y Acad Sci 2003, 1003: 250-72.
5. Pittenger, C., Sanacora, G., Krystal, J.H. The NMDA receptor as a therapeutic target in major depressive disorder. CNS Neurol Disord Drug Targets 2007, 6(2): 101-15.
6. O'Neill, M.J., Bleakman, D., Zimmerman, D.M., Nisenbaum, E.S. AMPA receptor potentiators for the treatment of CNS disorders. Curr Drug Targets CNS Neurol Disord 2004, 3(3); 181-94.
7. Lynch, G. Glutamate-based therapeutic approaches: Ampakines. Curr Opin Pharmacol 2006, 6(1): 82-8.
8. Lynch, G., Gall, C.M. Ampakines and the threefold path to cognitive enhancement. Trends Neurosci 2006, 29(10): 554-62.
9. Schoepp, D.D., Jane, D.E., Monn, J.A. Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology 1999, 38(10): 1431-76.
10. Pin, J.-P., De Colle, C., Bessis, A.-S., Acher, F. New perspectives for the development of selective metabotropic glutamate receptor ligands. Eur J Pharmacol 1999, 375(1-3): 277-94.
11. Pin, J.-P., Duvoisin, R. The metabotropic glutamate receptors: Structure and function. Neuropharmacology 1995, 34(1): 1-26.
12. Shigemoto, R., Wada, E., Ohishi, H., Takada, M., Mizuno, M., Roberts, J.D.B., Somogyi, P. Differential presynaptic localization of metabotropic glutamate receptor subtypes, mGluR2/3 and mGluR7 in the hippocampus. Soc Neurosci Abst 1995, 21: Abst 338.20.
13. Petralia, R.S., Wang, W.-X., Niedzielski, A.S., Wenthold, R.J. The metabotropic glutamate receptors, mGluR2 and mGluR3, show unique postsynaptic, presynaptic and glial localizations. Neuroscience 1996, 71(4): 949-76.
14. Ferraguti, F., Shigemoto, R. Metabotropic glutamate receptors. Cell Tissue Res 2006, 326(2): 483-504.
15. Bhave, G., Karim, F., Carlton, S.M., Gereau, R.W. 4th. Peripheral group I metabotropic glutamate receptors modulate nociception in mice. Nat Neurosci 2001, 4(4): 417-23.
16. Karim, F., Wang, C.C., Gereau, R.W. 4th. Metabotropic glutamate receptor subtypes 1 and 5 are activators of extracellular signal-regulated kinase signaling required for inflammatory pain in mice. J Neurosci 2001, 21(11): 3771-9.
17. Gasparini, F., Bilbe, G., Gomez-Mancilla, B., Spooren, W. mGluR5 antagonists: Discovery, characterization and drug development. Curr Opin Drug Discov Devel 2008, 11(5): 655-65.
18. Liu, F., Grauer, S., Kelley, C. et al. ADX47273 [S-(4-fluoro-phenyl)-{3- [3-(4-fluoro-phenyl)-[1,2,4]-oxadiazol-5-yl]-piperidin-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(3): 827-39.
19. Schlumberger, C., Pietraszek, M., Gravius, A., Klein, K.U., Greco, S., Morè, L., Danysz, W. 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(1-3): 73-83.
20. Schlumberger, C., Pietraszek, M., Gravius, A., Danysz, W. Effects of a positive allosteric modulator of mGluR5 ADX47273 on conditioned avoidance response and PCP-induced hyperlocomotion in the rat as models for schizophrenia. Pharmacol Biochem Behay 2010, 95(1): 23-30.
21. Steckler, T., Lavreysen, H., Oliveira, A.M. et al. Effects of mGlu1 receptor blockade on anxiety-related behaviour in the rat lick suppression test. Psychopharmacology (Berl) 2005, 179(1): 198-206.
22. Steckler, T., Oliveira, A.F., Van Dyck, C. et al. Metabotropic glutamate receptor 1 blockade impairs acquisition and retention in a spatial water maze task. Behav Brain Res 2005, 164(1): 52-60.
23. Shannon, H.E., Peters, S.C., Kingston, A.E. Anticonvulsant effects of LY456236, a selective mGlu1 receptpr antagonist. Neuropharmacology 2005, 49(Suppl. 1): 188-95.
24. Gasparini, F., Lingenhöhl K., Stoehr, N. et al. 2-Methyl-6- (phenylethynyl)- pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology 1999, 38(10): 1493-503.
25. Spooren, W.P., Gasparini, F., Bergmann, R., Kuhn, R. Effects of the prototypical mGlu(5) receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine on rotarod, locomotor activity and rotational responses in unilateral 6- OHDA-lesioned rats. Eur J Pharmacol 2000, 406(3): 403-10.
26. Spooren, W.P., Vassout, A., Neijt, H.C. et al. Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6- (phenylethynyl)pyridine in rodents. J Pharmacol Exp Ther 2000, 295(3): 1267-75.
27. Anderson, J.J., Rao, S.P., Rowe, B. et al. [3H]Methoxymethyl-3-[(2- methyl- 1,3-thiazol-4-yl)ethynyl]pyridine binding to metabotropic glutamate receptor subtype 5 in rodent brain: In vitro and in vivo characterization. J Pharmacol Exp Ther 2002, 303(3): 1044-51.
28. Cosford, N.D., Tehrani, L., Roppe, J. et al. 3-[(2-Methyl-1,3-thlozol-4- yl)ethynyl]-pyridine: A potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity. J Med Chem 2003, 46(2): 204-6.
29. Cosford, N.D., Roppe, J., Tehrani, L. et al. [3H]-Methoxymethyl-MTEP and [3H]-methoxy-PEPy: Potent and selective radioligands for the metabotropic glutamate subtype 5 (mGlu5) receptor. Bioorg Med Chem Lett 2003, 13(3): 351-4.
30. Schkeryantz, J.M., Kingston, A.E., Johnson, M.P. Prospects for metabotropic glutamate 1 receptor antagonists in the treatment of neuropathic pain. J Med Chem 2007, 50(11): 2563-8.
31. Hofmann, H.A., Siegling, A., Denzer, D., Spreyer, P., De Vry, J. Metabotropic glutamate mGlu1 receptor mRNA expression in dorsal root ganglia of rats after peripheral nerve injury. Eur J Pharmacol 2001, 429(1- 3): 135-8.
32. Zhou, S., Komak, S., Du, J., Carlton, S.M. Metabotropic glutamate 1alpha receptors on peripheral primary afferent fibers: Their role in nociception. Brain Res 2001, 913(1): 18-26.
33. Fundytus, M.E., Fischer, K., Dray, A., Henry, J.L., Coderre, T.J. In vivo antinociceptive activity of anti-rat mGluR1 and mGluR5 antibodies in rats. Neuroreport 1998, 9(4): 731-5.
34. Young, M.R., Blackburn-Munro, G., Dickinson, T., Johnson, M.J., Anderson, H., Nakalembe, I., Fleetwood-Walker, S.M. Antisense ablation of type I metabotropic glutamate receptor mGluR1 inhibits spinal nociceptive transmission. J Neurosci 1998, 18(23): 10180-8. (Pubitemid 28543791)
35. Fundytus, M.E., Osborne, M.G., Henry, J.L., Coderre, T.J., Dray, A. Antisense oligonucleotide knockdown of mGluR1 alleviates hyperalgesia and allodynia associated with chronic inflammation. Pharmacol Biochem Behav 2002, 73(2): 401-10.
36. Zhu, C.Z., Baker, S., El-Kouhen, O. et al. Analgesic activity of metabotropic glutamate receptor 1 antagonists on spontaneous post-operative pain in rats. Eur J Pharmacol 2008, 580(3): 314-21.
37. Varty, G.B., Grilli, M., Fortani, A. et al. The antinociceptive and anxiolytic- like effects of the metabotropic glutamate receptor 5 (mGluR5) antagonists, MPEP and MTEP, and the mGluR1 antagonist, LY456236, in rodents: a comparison of efficacy and side-effect profiles. Psychopharmacology (Berl) 2005, 179(1): 207-17.
38. Sevostianova, N., Danysz, W. Analgesic effects of mGlu1 and mGlu5 receptor antagonists in the rat formalin test. Neuropharmacology 2006, 51(3): 623-30.
39. Ichise, T., Kano, M., Hashimoto, K. et al. mGluR1 in cerebellar Purkinje cells essential for long-term depression, synapse elimination, and motor coordination. Science 2000, 288(5472): 1832-5.
40. El-Kouhen, O., Lehto, S.G., Pan, J.B. et al. Blockade of mGluR1 receptor results in analgesia and disruption of motor and cognitive performances: Effects of A-841720, a novel non-competitive mGluR1 receptor antagonist. Br J Pharmacol 2006, 149(6): 761-74.
41. Brodkin, J., Bradbury, M., Busse, C., Warren, N., Bristow, L.J., Varney, M.A. Reduced stress-induced hyperthermia in mGluR5 knockout mice. Eur J Neurosci 2002, (11): 2241-4.
42. Brodkin, J., Busse, C., Sukoff, S.J., Varney, M.A. Anxiolytic-like activity of the mGluR5 antagonist MPEP a comparison with diazepam and buspirone. Pharmacol Biochem Behav 2002, 73(2): 359-66.
43. Tatarczynska, E., Klodzinska, A., Chojnacka-Wojcik, E., Palucha, A., Gasparini, F., Kuhn, R., Pilc, A. Potential anxiolytic- and antidepressant- like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. Br J Pharmacol 2001, 132(7): 1423-30. (Pubitemid 32281030)
44. Roppe, J.R., Wang, B., Huang, D. et al. 5-[(2-Methyl-1,3-thiazol-4- yl)ethynyl]-2,3′-bipyridine: A highly potent, orally active metabotropic glutamate subtype 5 (mGlu5) receptor antagonist with anxiolytic activity. Bioorg Med Chem Lett 2004, 14(15): 3993-6.
45. Busse, C.S., Brodkin, J., Tattersall, D. et al. The behavioral profile of the potent and selective mGlu5 receptor antagonist 3-[(2-methyl-1,3-thiazol-4- yl)ethynyl]pyridine (MTEP) in rodent models of anxiety. Neuropsychopharmacology 2004, 29(11): 1971-9.
46. Ballard, T.M., Woolley, M.L., Prinssen, E., Huwyler, J., Porter, R., Spooren, W. The effect of the mGlu5 receptor antagonist MPEP in rodent tests of anxiety and cognition: A comparison. Psychopharmacology (Berl) 2005, 179(1): 218-29.
47. Pecknold, J.C., McClure, D.J., Appeltauer, L., Wrzesinski, L., Allan, T. Treatment of anxiety using fenobam (a nonbenzodiazepine) in a double- blind standard (diazepam) placebo-controlled study. J Clin Psychopharmacol 1982, 2(2): 129-33.
48. Porter, R.H., Jaeschke, G., Spooren, W. et al. Fenobam: A clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with Inverse agonist activity. J Pharmacol Exp Ther 2005, 315(2): 711-21.
49. Wieronska, J.M., Szewczyk, B., Branski, P., Palucha, A., Pilc, A. Antidepressant-like effect of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist in the olfactory bulbectomized rots. Amino Acids 2002, 23(1-3): 213-6.
50. Palucha, A., Branski, P., Szewczyk, B., Wieronska, J.M., Klak, K., Pilc, A. Potential antidepressant-like effect of MTEP, a potent and highly selective mGluR5 antagonist. Pharmacol Biochem Behav 2005, 81(4): 901-6.
51. Li, X., Need, A.B., Baez, M., Witkin, J.M. Metabotropic glutamate 5 receptor antagonism is associated with antidepressant-like effects in mice. J Pharmacol Exp Ther 2006, 319(1): 254-9.
52. Belozertseva, I.V., Kos, T., Popik, P., Danysz, W., Bespatov, A.Y. Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced swim and the mouse tall suspension tests. Eur Neuropsychopharmacol 2007, 17(3): 172-9.
53. Treyer, V., Streffer, J., Ametamey, S.M. et al. Radiation dosimetry and biodistribution of 11C-ABP688 measured in healthy volunteers. Eur J Nucl Med Mol Imaging 2008, 35(4): 766-70.
54. Conn, P.J., Battaglia, G., Marino, M.J., Nicoletti, F. Metabotropic glutamate receptors in the basal ganglia motor circuit. Nat Rev Neurosci 2005, 6(10): 787-98.
55. Blandini, F., Greenamyre, J.T. Prospects of glutamate antagonists in the therapy of Parkinson's disease. Fundam Clin Pharmacol 1998, 12(1): 4-12.
56. Greenamyre, J.T., Elter, R.V., Zhang, Z., Ovadia, A., Kurlan, R., Gash, D.M. Antiparkinsonian effects of remacemide hydrochloride, a glutamate antagonist, in rodent and primate models of Parkinson's disease. Ann Neurol 1994, 35(6): 655-61.
57. Testa, C.M., Standaert, D.G., Young, A.B., Penney, J.B. Jr. Metabotropic glutamate receptor mRNA expression in the basal ganglia of the rat. J Neurosci 1994, 14(5, Pt. 2): 3005-18.
58. Awad, H., Hubert, G.W., Smith, Y., Levey, A.I., Conn, P.J. Activation of metabotropic glutamate receptor 5 has direct excitatory effects and potentiates NMDA receptor currents in neurons of the subthalamic nucleus. J Neurosci 2000, 20(21): 7871-9.
59. Marino, M.J., Wittmann, M., Bradley, S.R., Hubert, G.W., Smith, Y., Conn, P.J. Activation of group I metabotropic glutamate receptors produces a direct excitation and disinhibition of GABAergic projection neurons in the substantia nigra pars reticulata. J Neurosci 2001, 21(18): 7001-12.
60. Sanchez-Pernaute, R., Wang, J.Q., Kuruppu, D. et al. Enhanced binding of metabotropic glutamate receptor type 5 (mGluR5) PET tracers in the brain of parkinsonian primates. Neuroimage 2008, 42(1): 248-51.
61. Breysse, N., Baunez, C., Spooren, W., Gasparini, F., Amalric, M. Chronic but not acute treatment with a metabotropic glutamate 5 receptor antagonist reverses the akinetic deficits in a rat model of parkinsonism. J Neurosci 2002, 22(13): 5669-78.
62. Breysse, N., Amalric, M., Salin, P. Metabotropic glutamate 5 receptor blockade alleviates akinesia by normalizing activity of selective basal-ganglia structures in parkinsonian rats. J Neurosci 2003, 23(23): 8302-9.
63. Phillips, J.M., Lam, H.A., Ackerson, L.C., Maidment, N.T. Blockade of mGluR glutamate receptors in the subthalamic nucleus ameliorates motor asymmetry in an animal model of Parkinson's disease. Eur J Neurosci 2006, 23(1): 151-60.
64. Ismayilova, N., Verkhratsky, A., Dascombe, M.J. Changes in mGlu5 receptor expression in the basal ganglia of reserpinised rats. Eur J Pharmacol 2006, 545(2-3): 134-41.
65. Pellegrino, D., Cicchetti, F., Wang, X., Zhu, A., Yu, M., Saint-Pierre, M., Brownell, A.L. Modulation of dopaminergic and glutamatergic brain function: PET studies on parkinsonian rats. J Nucl Med 2007, 48(7): 1147-53.
66. Zhu, A., Wang, X., Yu, M., Wang, J.Q., Brownell, A.L. Evaluation of four pyridine analogs to characterize 6-OHDA-induced modulation of mGluR5 function in rat brain using microPET studies. J Cereb Blood Flow Metab 2007, 27(9): 1623-31.
67. Ossowska, K., Konieczny, J., Wolfarth, S., Wieronska, J., Pilc, A. Blockade of the metabotropic glutamate receptor subtype 5 (mGluR5) produces antiparkinsonian-like effects in rats. Neuropharmacology 2001, 41(4): 413-20.
68. Ossowska, K., Konieczny, J., Wolfarth, S., Pilc, A. MTEP, a new selective antagonist of the metabotropic glutamate receptor subtype 5 (mGluR5), produces antiparkinsonian-like effects in rats. Neuropharmacology 2005, 49(4): 447-55.
69. Dekundy, A., Pietraszek, M., Schaefer, D., Cenci, M.A., Danysz, W. Effects of group I metabotropic glutamate receptors blockade in experimental models of Parkinson's disease. Brain Res Bull 2006, 69(3): 318-26.
70. Mela, F., Marti, M., Dekundy, A., Danysz, W., Morari, M., Cenci, M.A. Antagonism of metabotropic glutamate receptor type 5 attenuates l- DOPA-induced dyskinesia and its molecular and neurochemical correlates in a rat model of Parkinson's disease. J Neurochem 2007, 101(2): 483-97.
71. Levandis, G., Bazzini, E., Armentero, M.T., Nappi, G., Blandini, F. Systemic administration of an mGluR5 antagonist, but not unilateral subthalamic lesion, counteracts l-DOPA-induced dyskinesias in a rodent model of Parkinson's disease. Neurobiol Dis 2008, 29(1): 161-8.
72. Rylander, D., Recchia, A., Mela, F., Dekundy, A., Danysz, W., Cenci, M.A. Pharmacological modulation of glutamate transmission in a rat model of L-DOPA-induced dyskinesia: Effects on motor behavior and striatal nuclear signaling. J Pharmacol Exp Ther 2009, 330(1): 227-35.
73. Gravius, A., Dekundy, A., Nagel, J., Morè, L., Pietraszek, M., Danysz, W. Investigation on tolerance development to subchronic blockade of mGluR5 in models of learning, anxiety, and levodopa-induced dyskinesia in rats. J Neural Transm 2008, 115(12): 1609-19.
74. Samadi, P., Grégoire, L., Morissette, M. et al. mGluR5 metabotropic glutamate receptors and dyskinesias in MPTP monkeys. Neurobiol Aging 2008, 29(7): 1040-51.
75. Morin, N., Grégoire, L., Gomez-Mancilla, B., Gasparini, F., Di Paolo, T. Effect of the metabotropic glutamate receptor type 5 antagonists MPEP and MTEP in parkinsonian monkeys. Neuropharmacology 2010, 58(7): 981-6.
76. Golembiowska, K., Konieczny, J., Wolfarth, S., Ossowska, K. Neuroprotective action of MPEP, a selective mGluR5 antagonist, in methamphetamine-induced dopaminergic neurotoxicity is associated with a decrease in dopamine outflow and inhibition of hyperthermia in rats. Neuropharmacology 2003, 45(4): 484-92.
77. Battaglia, G., Busceti, C.L., Molinaro, G. et al. Endogenous activation of mGlu5 metabotropic glutamate receptors contributes to the development of nigro-striatal damage induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. J Neurosci 2004, 24(4): 828-35.
78. Armentero, M.T., Fancellu, R., Nappi, G., Bramanti, P., Blandini, F. Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson's disease. Neurobiol Dis 2006, 22(1): 1-9.
79. Vernon, A.C., Palmer, S., Datla, K.P., Zbarsky, V., Croucher, M.J., Dexter, D.T. Neuroprotective effects of metabotropic glutamate receptor ligands in a 6-hydroxydopamine rodent model of Parkinson's disease. Eur J Neurosci 2005, 22(7): 1799-806.
80. Vernon, A.C., Zbarsky, V., Datla, K.P., Croucher, M.J., Dexter, D.T. Subtype selective antagonism of substantia nigra pars compacta group I metabotropic glutamate receptors protects the nigrostriatal system against 6-hydroxydopamine toxicity in vivo. J Neurochem 2007, 103(3): 1075-91.
81. Olney, J.W., Farber, N.B. Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry 1995, 52(12): 998-1007.
82. Olney, J.W., Newcomer, J.W., Farber, N.B. NMDA receptor hypofunction model of schizophrenia. J Psychiatr Res 1999, 33(6): 523-33.
83. Weinberger, D.R. Schizophrenia drug says goodbye to dopamine. Nat Med 2007, 13(9): 1018-9.
84. Andine, P., Widermark, N., Axelsson, R., Nyberg, G., Olofsson, U., Martensson, E., Sandberg, M. Characterization of MK-801-induced behavior as a putative rat model of psychosis. J Pharmacol Exp Ther 1999, 290(3): 1393-408.
85. Javitt, D.C., Zukin, S.R. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 1991, 148(10): 1301-8.
86. Krystal, J.H., Belger, A., D'Souza, C., Anand, A., Charney, D.S., Aghajanian, G.K., Moghaddam, B. Therapeutic implications of the hyperglutamatergic effects of NMDA antagonists. Neuropsychopharmacology 1999, 21: S143-7.
87. Lahti, A.C., Holcomb, H.H., Gao, X.M., Tamminga, C.A. NMDA-sensitive glutamate antagonism: A human model of psychosis. Neuropsychopharmacology 1999, 22: S158-69.
88. Holcomb, H.H., Lahti, A.C., Medoff, D.R., Cullen, T., Tamminga, C.A. Effects of noncompetitive NMDA receptor blockade on anterior cingulate cerebral blood flow in volunteers with schizophrenia. Neuropsychopharmacology 2005, 30: 2275-82.
89. Cartmell, J., Schoepp, D.D. Regulation of neurotransmitter release by metabotropic glutamate receptors. J Neurochem 2000, 75(3): 889-907.
90. Schoepp, D.D. Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system. J Pharmacol Exp Ther 2001, 299(1): 12-20.
91. Conn, P.J., Pin, J.P. Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 1997, 37: 205-37.
92. Bruno, V., Battaglia, G., Casabona, G., Copani, A., Caciagli, F., Nicoletti, F. Neuroprotection by glial metabotropic glutamate receptors is mediated by transforming growth factor-beta. J Neurosci 1998, 18(23): 9594-600.
93. Wright, R.A., Arnold, M.B., Wheeler, W.J., Ornstein, P.L., Schoepp, D.D. [3H]LY341495 binding to group II metabotropic glutamate receptors in rat brain. J Pharmacol Exp Ther 2001, 298(2): 453-60.
94. Monn, J.A., Valli, M.J., Johnson, B.G. et al. Synthesis of the four isomers of 4-aminopyrrolidine-2,4-dicarboxylate: Identification of a potent, highly selective, and systemically-active agonist for metabotropic glutamate receptors negatively coupled to adenylate cyclase. J Med Chem 1996, 39(15): 2990-3000.
95. Monn, J.A., Valli, M.J., Massey, S.M. et al. Synthesis, pharmacological characterization, and molecular modeling of heterobicyclic amino acids related to (+)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylic acid (LY354740): Identification of two new potent, selective, and systemically active agonists for group II metabotropic glutamate receptors. J Med Chem 1999, 42(6): 1027-40.
96. Monn, J.A., Valli, M.J., Massey, S.M. et al. Design, synthesis, and pharmacological characterization of (+)-2-aminobicyclo[3.1.0]hexane-2,6- dicarboxylic acid (LY354740): A potent, selective, and orally active group 2 metabotropic glutamate receptor agonist possessing anticonvulsant and anxiolytic properties. J Med Chem 1997, 40(4): 528-37.
97. Monn, J.A., Massey, S.M., Valli, M.J. et al. Synthesis and metabotropic glutamate receptor activity of S-oxidized variants of (-)-4-amino-2-thiabicyclo- [3.1.0]hexane-4,6-dicarboxylate: Identification of potent, selective, and orally bioavailable agonists for mGlu2/3 receptors. J Med Chem 2007, 50(2): 233-40.
98. Nakazato, A., Kumagai, T., Sakagami, K. et al. Synthesis, SARs, and pharmacological characterization of 2-amino-3 or 6-fluorobicyclo[3.1.0]hexane-2, 6-dicarboxylic acid derivatives as potent, selective, and orally active group II metabotropic glutamate receptor agonists. J Med Chem 2000, 43(25): 4893-909.
99. Rorick-Kehn, L.M., Johnson, B.G., Burkey, J.L. 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(1): 308-17.
100. Nakki, R., Sharp, F.R., Sagar, S.M., Honkaniemi, J. Effects of phencyclidine on immediate early gene expression in the brain. J Neurosci Res 1996, 45(1): 13-27.
101. Danysz, W., Essmann, U., Bresink, I., Wilke, R. Glutamate antagonists have different effects on spontaneous locomotor activity in rats. Pharmacol Biochem Behav 1994, 48(1): 111-8.
102. Moghaddam, B., Adams, B., Verma, A., Daly, D. Activation of glutamatergic neurotransmission by ketamine: A novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci 1997, 17(8): 2921-7.
103. Danysz, W., Wroblewski, J.T., Costa, E. Learning impairment in rats by N- methyl-D-aspartate receptor antagonists. Neuropharmacology 1988, 27(6): 653-6.
104. Parada-Turska, J., Turski, W.A. Excitatory amino acid antagonists and memory: Effect of drugs acting at N-methyl-D-aspartate receptors in learning and memory tasks. Neuropharmacology 1990, 29(12): 1111-6.
105. Moghaddam, B., Adams, B.W. Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science 1998, 281: 1349-52.
106. Cartmell, J., Monn, J.A., Schoepp, D.D. 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(1): 161-70.
107. Cartmell, J., Monn, J.A., Schoepp, D.D. Attenuation of specific PCP- evoked behaviors by the potent mGlu2/3 receptor agonist, LY379268 and comparison with the atypical antipsychotic, clozapine. Psychopharmacology (Berl) 2000, 148(4): 423-9.
108. Cartmell, J., Monn, J.A., Schoepp, D.D. Tolerance to the motor impairment, but not to the reversal of PCP-induced motor activities by oral administration of the mGlu2/3 receptor agonist, LY379268. Naunyn Schmiedebergs Arch Pharmacol 2000, 361(1): 39-46.
109. Swanson, C.J., Schoepp, D.D. The group II metabotropic glutamate receptor agonist (-)-2-oxa-4-aminobicyclo[3.1.0.]hexane-4,6-dicarboxylate (LY379268) and clozapine reverse phencyclidine-induced behaviors in monoamine-depleted rats. J Pharmacol Exp Ther 2002, 303(3): 919-27.
110. Swanson, C.J., Schoepp, D.D. A role for noradrenergic transmission in the actions of phencyclidine and the antipsychotic and antistress effects of mGlu2/3 receptor agonists. Ann N Y Acad Sci 2003, 1003: 309-17.
111. Rorick-Kehn, L.M., Johnson, B.G., Knitowski, K.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 (Bert) 2007, 193(1): 121-36.
112. Lorrain, D.S., Baccei, C.S., Bristow, L.J., Anderson, J.J., Varney, M.A. Effects of ketamine and N-methyl-D-aspartate on glutamate and dopamine release in the rat prefrontal cortex: Modulation by a group II selective metabotropic glutamate receptor agonist LY379268. Neuroscience 2003, 117(3): 697-706.
113. Greenslade, R.G., Mitchell, S.N. Selective action of (-)-2-oxa-4- aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268), a group II metabotropic glutamate receptor agonist, on basal and phencyclidine-induced dopamine release in the nucleus accumbens shell. Neuropharmacology 2004, 47(1): 1-8.
114. Fell, M.J., Katner, J.S., Johnson, B.G., Perry, K.W., Svensson, K.A. Differential effects of the mGlu2/3 receptor agonist LY379268 and clozapine on ketamine evoked locomotor activity and neurotransmitter release in the rat brain. Neuropharmacology 2008, 55(4): 595.
115. Gozzi, A., Large, C.H., Schwarz, A., Bertani, S., Crestan, V., Bifone, A. Differential effects of antipsychotic and glutamatergic agents on the phMRI response to phencyclidine. Neuropsychopharmacology 2008, 33(7): 1690-703.
116. Schreiber, R., Lowe, D., Voerste, A., De Vry, J. LY354740 affects startle responding but not sensorimotor gating or discriminative effects of phencyclidine. Eur J Pharmacol 2000, 388(2): R3-4.
117. Ossowska, K., Pietraszek, M., Wardas, J., Nowak, G., Zajaczkowski, W., Wolfarth, S., Pilc, A. The role of glutamate receptors in antipsychotic drug action. Amino Acids 2000, 19(1): 87-94.
118. Auclair, A., Cotecchia, S., Glowinski, J., Tassin, J.P. D-Amphetamine falls to increase extracellular dopamine levels in mice lacking alpha 1b-adrenergic receptors: Relationship between functional and nonfunctional dopamine release. J Neurosci 2002, 22(21): 9150-4.
119. Ellenbroek, B.A. Treatment of schizophrenia: A clinical and preclinical evaluation of neuroleptic drugs. Pharmacol Ther 1993, 57(1): 1-78.
120. Cartmell, J., Monn, J.A., Schoepp, D.D. The mGlu(2/3) receptor agonist LY379268 selectively blocks amphetamine ambulations and rearing. Eur J Pharmacol 2000, 400(2-3): 221-4.
121. Fell, M.J., Perry, K.W., Falcone, J.F. et al. In vitro and in vivo evidence for a lack of interaction with dopamine D2 receptors by the metabotropic glutamate 2/3 receptor agonists 1S,2S,5R,6S-2-aminobicyclo[3.1.0] hexane- 2,6-bicarboxylate monohydrate (LY354740) and (-)-2-oxa-4-amlnobicyclo[3. 1.0]hexane-4,6-dicarboxylic acid (LY379268). J Pharmacol Exp Ther 2009, 331(3): 1126-36.
122. Taber, M.T., Fibiger, H.C. Electrical stimulation of the prefrontal cortex increases dopamine release in the nucleus accumbens of the rat: Modulation by metabotropic glutamate receptors. J Neurosci 1995, 15(5, Pt. 2): 3896-904.
123. Meltzer, H.Y. Mechanism of action of atypical antipsychotic drugs. In: Neuropsychopharmacology: The Fifth Generation of Progress. K.L. Davis, D. Charney, J.T. Coyle, C. Nemeroff (Eds.). Lippincott Williams & Wilkins, 2002, 819-31.
124. Marek, G.J., Wright, R.A., Schoepp, D.D., Monn, J.A., Aghajanian, G.K. Physiological antagonism between 5-hydroxytryptamine(2A) and group II metabotropic glutamate receptors in prefrontal cortex. J Pharmacol Exp Ther 2000, 292(1): 76-87.
125. Gewirtz, J.C., Marek, G.J. Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors. Neuropsychopharmacology 2000, 23(5): 569-76.
126. Zhai, Y., George, C.A., Zhai, J., Nisenbaum, E.S., Johnson, M.P., Nisenbaum, L.K. Group II metabotropic glutamate receptor modulation of DOI-induced c-fos mRNA and excitatory responses in the cerebral cortex. Neuropsychopharmacology 2003, 28(1): 45-52.
127. Cartmell, J., Perry, K.W., Salhoff, C.R., Monn, J.A., Schoepp, D.D. The potent, selective mGlu2/3 receptor agonist LY379268 increases extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindole-3-acetic acid in the medial prefrontal cortex of the freely moving rat. J Neurochem 2000, 75(3): 1147-54.
128. Johnson, M.P., Baez, M., Jagdmann, G.E. Jr. 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(15): 3189-92.
129. Schaffhauser, H., Rowe, B.A., Morales, S. et al. Pharmacological characterization and identification of amino acids involved in the positive modulation of metabotropic glutamate receptor subtype 2. Mol Pharmacol 2003, 64(4): 798-810.
130. Pinkerton, A.B., Vernier, J.M., Schaffhauser, H. et al. Phenyl-tetrazolyl acetophenones: Discovery of positive allosteric potentiatiors for the metabotropic glutamate 2 receptor. J Med Chem 2004, 47(18): 4595-9.
131. Bonnefous, C., Vernier, J.M., Hutchinson, J.H. et al. Biphenyl-indanones: Allosteric potentiators of the metabotropic glutamate subtype 2 receptor. Bioorg Med Chem Lett 2005, 15(19): 4354-8.
132. Galici, R., Jones, C.K., Hemstapat, K. et al. Biphenyl-indanone A, a positive allosteric modulator of the metabotropic glutamate receptor subtype 2, has antipsychotic- and anxiolytic-like effects in mice. J Pharmacol Exp Ther 2006, 318(1): 173-85.
133. Jones, C.K., Xiang, Z., Jones, P.J. et al. Novel allosteric modulators of metabotropic glutamate receptors subtypes 2 and 5 for the treatment of schizophrenia. Neuropharmacology 2008, 55(4): 603.
134. Spooren, W.P.J.M., Gasparini, F., van der Putten, H., Koller, M., Nakanishi, S., Kuhn, R. Lack of effect of LY314582 (a group 2 metabotropic glutamate receptor agonist) on phencyclidine-induced locomotor activity in metabotropic glutamate receptor 2 knockout mice. Eur J Pharmacol 2000, 397(1): R1-2.
135. Fell, M.J., Svensson, K.A., Johnson, B.G., Schoepp, D.D. Evidence for the role of mGlu2 not mGlu3 receptors in the pre-clinical 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(1): 209-17.
136. Woolley, M.L., Pemberton, D.J., Bate, S., Corti, C., Jones. D.N. 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(3): 431-40.
137. Patil, S.T., Zhang, L., Martenyi, F. et al. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: A randomized phase 2 clinical trial. Nat Med 2007, 1(9): 1102-7.
138. Schoepp, D.D., Wright, R., Levine, L.R., Gaydos, B., Potter, W.Z. LY354740, an mGlu2/3 receptor agonist as a novel approach to treat anxiety/stress. Stress 2003, 6(3): 189-97.
139. Swanson, C.J., Bures, M., Johnson, M.P., Linden, A.M., Monn, J.A., Schoepp, D.D. Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nat Rev Drug Discov 2005, 4(2): 131-44.
140. Zarate, C.A. Jr., Singh, J.B., Carlson, P.J. et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006, 63(8): 856-64.
141. Valentine, G.W., Sanacora, G. Targeting glial physiology and glutamate cycling in the treatment of depression. Biochem Pharmacol 2009, 78(5): 431-9.
142. Witkin, J.M., Eiler, W.J.A. Antagonism of metabotropic glutamate group II receptors in the potential treatment of neurological and neuropsychiatric disorders. Drug Dev Res 2006, 67: 757-69.
143. Alt, A., Nisenbaum, E.S., Bleakman, D., Witkin, J.M. A role for AMPA receptors in mood disorders. Biochem Pharmacol 2006, 71(9): 1273-88.
144. Skolnick, P. AMPA receptors: A target for novel antidepressants? Biol Psychiatry 2008, 63(4): 347-8.
145. Pilc, A., Chaki, S., Nowak, G., Witkin, J.M. Mood disorders: Regulation by metabotropic glutamate receptors. Biochem Pharmacol 2008, 75(5): 997-1006.
146. Witkin, J.M., Marek, G.J., Johnson, B.G., Schoepp, D.D. Metabotropic glutamate receptors in the control of mood disorders. CNS Neurol Disord Drug Targets 2007, 6(2): 87-100.
147. Ohishi, H., Shigemoto, R., Nakanishi, S., Mizuno, N. Distribution of the messenger RNA for a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat. Neuroscience 1993, 53(4): 1009-18.
148. Tanabe, Y., Nomura, A., Masu, M., Shigemoto, R., Mizuno, N., Nakanishi, S. Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4. J Neurosci 1993, 13(4): 1372-8.
149. Banasr, M., Chowdhury, G.M., Terwilliger, R., Newton, S.S., Duman, R.S., Behar, K.L., Sanacora, G. Glial pathology in an animal model of depression: Reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Mol Psychiatry 2008, Epub ahead of print.
150. Shigemoto, R., Kinoshita, A., Wada, E. et al. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. J Neurosci 1997, 17(19): 7503-22.
151. Ohishi, H., Shigemoto, R., Nakanishi, S., Mizuno, N. Distribution of the mRNA for a metabotropic glutamate receptor (mGluR3) in the rat brain: An in situ hybridization study. J Comp Neurol 1993, 335(2): 252-66.
152. Kingston, A.E., Ornstein, P.L., Wright, R.A. et al. LY341495 is a nanomolar potent and selective antagonist of group II metabotropic glutamate receptors. Neuropharmacology 1998, 37(1): 1-12.
153. Chaki, S., Yoshikawa, R., Hirota, S. et al. MGS0039: A potent and selective group II metabotropic glutamate receptor antagonist with antidepressant-like activity. Neuropharmacology 2004 46(4): 457-67.
154. Nakazato, A., Sakagami, K., Yasuhara, A. et al. Synthesis, in vitro pharmacology, structure-activity relationships, and pharmacokinetics of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as potent and selective group II metabotropic glutamate receptor antagonists. J Med Chem 2004, 47(18): 4570-87.
155. Nakamura, M., Kawakita, Y., Yasuhara, A., Fukasawa, Y., Yoshida, K., Sakagami, K., Nakazato, A. In vitro and in vivo evaluation of the metabolism and bioavailability of esterprodrugs of MGS0039 (3-(3,4-dichlorobenzyloxy)-2-amino- 6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid), a potent metabotropic glutamate receptor antagonist. Drug Metab Dispos 2006, 34(3): 369-74.
156. Yasuhara, A., Nakamura, M., Sakagami, K. et al. Prodrugs of 3-(3,4-dichlorobenzyloxy)-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (MGS0039): A potent and orally active group II mGluR antagonist with antidepressant-like potential. Bioorg Med Chem 2006, 14(12): 4193-207.
157. Hemstapat, K., Da Costa, H., Nong, Y. et al. A novel family of potent negative allosteric modulators of group II metabotropic glutamate receptors. J Pharmacol Exp Ther 2007, 322(1): 254-64.
158. Woltering, T.J., Wichmann, J., Goetschi, E. et al. Synthesis and characterization of 1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives: Part 3. New potent non-competitive metabotropic glutamate receptor 2/3 antagonists. Bioorg Med Chem Lett 2008, 18(8): 2725-9.
159. Kawashima, N., Karasawa, J., Shimazaki, T., Chaki, S., Okuyama, S., Yasuhara, A., Nakazato, A. Neuropharmacological profiles of antagonists of group II metabotropic glutamate receptors. Neurosci Lett 2005, 378(3): 131-4.
160. Karasawa, J., Yoshimizu, T., Chaki, S. A metabotropic glutamate 2/3 receptor antagonist, MGS0039, increases extracellular dopamine levels in the nucleus accumbens shell. Neurosci Lett 2006, 393(2-3): 127-30.
161. Morishima, Y., Miyakawa, T., Furuyashiki, T., Tanaka, Y., Mizuma, H., Nakanishi, S. Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice. Proc Natl Acad Sci U S A 2005, 102(11): 4170-5.
162. Santarelli, L., Saxe, M., Gross, C. et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003, 301(5634): 805-9.
163. Alt, A., Witkin, J.M., Bleakman, D. AMPA receptor potentiators as novel antidepressants. Curr Pharm Des 2005, 11(12): 1511-27.
164. Duman, R.S., Nakagawa, S., Malberg, J. Regulation of adult neurogenesis by antidepressant treatment. Neuropsychopharmacology 2001, 25(6): 836-44.
165. Yoshimizu, T., Chaki, S. Increased cell proliferation in the adult mouse hippocampus following chronic administration of group II metabotropic glutamate receptor antagonist, MGS0039. Biochem Biophys Res Commun 2004, 315(2): 493-6.
166. Bespalov, A.Y., van Gaalen, M.M., Sukhotina, I.A., Wicke, K., Mezler, M., Schoemaker, H., Gross, G. Behavioral characterization of the mGlu group II/III receptor antagonist, LY-341495, in animal models of anxiety and depression. Eur J Pharmacol 2008, 592(1-3): 96-102.
167. Yoshimizu, T., Shimazaki, T., Ito, A., Chaki, S. An mGluR2/3 antagonist, MGS0039, exerts antidepressant and anxiolytic effects in behavioral models in rats. Psychopharmacology (Berl) 2006, 186(4): 587-93.
168. Kenny, P.J., Gasparini, F., Markou, A. Group II metabotropic and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate glutamate receptors regulate the deficit in brain reward function associated with nicotine withdrawal in rats. J Pharmacol Exp Ther 2003, 306(3): 1068-76.
169. Matrisciano, F., Storto, M., Ngomba, R.T. Imipramine treatment up-regulates the expression and function of mGlu2/3 metabotropic glutamate receptors in the rat hippocampus. Neuropharmacology 2002, 42(8): 1008-15.
170. Matrisciano, F., Scaccianoce, S., Del Bianco, P. Metabotropic glutamate receptors and neuroadaptation to antidepressants: Imipramine-induced down-regulation of beta-adrenergic receptors in mice treated with metabotropic glutamate 2/3 receptor ligands. J Neurochem 2005, 93(5): 1345-52.
171. Karasawa, J., Shimazaki, T., Kawashima, N., Chaki, S. AMPA receptor stimulation mediates the antidepressant-like effect of a group II metabotropic glutamate receptor antagonist. Brain Res 2005, 1042(1): 92-8.
172. Bleakman, D., Alt, A., Witkin, J.M. AMPA receptors in the therapeutic management of depression. CNS Neurol Disord Drug Targets 2007, 6(2): 117-26.
173. Zarate. C.A. Jr., Manji, H.K. The role of AMPA receptor modulation in the treatment of neuropsychiatric diseases. Exp Neurol 2008, 211(1): 7-10.
174. Engers, D.W., Niswender, C.M., Weaver, C.D. et al. Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs). J Med Chem 2009, 52(14): 4115-8.
175. Williams, R., Niswender, C.M., Luo, Q., Le, U., Conn, P.J., Lindsley, C.W. Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead. Bioorg Med Chem Lett 2009, 19(3): 962-6.
176. Niswender, C.M., Lebois, E.P., Luo, Q. et al. Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4): Part I. Discovery of pyrazolo[3,4-d]pyrimidines as novel mGluR4 positive allosteric modulators. Bioorg Med Chem Lett 2008, 18(20): 5626-30.
177. Cryan, J.R., Kelly, P.H., Neijt, H.C., Sansig, G., Flor, P.J., van Der Putten, H. Antidepressant and anxiolytic-like effects in mice lacking the group III metabotropic glutamate receptor mGluR7. Eur J Neurosci 2003, (11): 2409-17.
178. Mitsukawa, K., Yamamoto, R., Ofner, S. et al. A selective metabotropic glutamate receptor 7 agonist: Activation of receptor signaling via an allosteric site modulates stress parameters in vivo. Proc Natl Acad Sci U S A 2005, 102(51): 18712-7.
179. Bradley, S.R., Standaert, D.G., Rhodes, K.J., Rees, H.D., Testa, C.M., Levey, A.I., Conn, P.J. Immunohistochemical localization of subtype 4a metabotropic glutamate receptors in the rat and mouse basal ganglia. J Comp Neurol 1999, 407(1): 33-46.
180. Messenger, M.J., Dawson, L.G., Duty, S. Changes in metabotropic receptor 1-8 gene expression in the rodent basal ganglia motor loop following lesion of the nigrostriatal tract. Neuropharmacology 2002, 43(2): 261-71.
181. Rodriguez, M.C., Obeso, J.A., Olanow, C.W. Subthalamic nucleus-mediated excitotoxicity in Parkinson's disease: A target for neuroprotection. Ann Neurol 1998, 44(3, Suppl. 1): S175-88.
182. Valenti, O., Marino, M.J., Wittman, M., Lis, E., DiLella, A.G., Kinney, G.G., Conn, P.J. Croup III metabotropic glutamate receptor-mediated modulation of the striatopallidal synapse. J Neurosci 2003, 23(18): 7218-26.
183. MacInnes, N., Messenger, M.J., Duty, S. Activation of group III metabotropic glutamate receptors in selected regions of the basal ganglia alleviates akinesia in the reserpine-treated rat. Br J Pharmacol 2004, 141(1): 15-22.
184. Maj, M., Bruno, V., Dragic, Z. et al. (-)-PHCCC, a positive allosteric modulator of mGluR4: Characterization, mechanism of action, and neuroprotection. Neuropharmacology 2003, 45(7): 895-906.
185. Marino, M.J., Williams, D.L. Jr., O'Brien, J.A. et al. Allosteric modulation of group III metabotropic glutamate receptor 4: A potential approach to Parkinson's disease treatment. Proc Natl Acad Sci U S A 2003, 100(23): 13668-73.
186. Niswender, C.M., Johnson, K.A., Weaver, C.D. et al. Discovery, characterization and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4. Mol Pharmacol 2008, 74(5): 1345-58.
187. Matsui, T., Kita, H. Activation of group III metabotropic glutamate receptors presynaptically reduces both GABAergic and glutamatergic transmission in the rat globus pallidus. Neuroscience 2003, 122(3): 727-37.
188. Wigmore, M.A., Lacey, M.G.. Metabotropic glutamate receptors depress glutamate-mediated synaptic input to rat midbrain dopamine neurones in vitro. Br J Pharmacol 1998, 123(4): 667-74.
189. Valenti, O., Mannaioni, G., Seabrook, G.R., Conn, P.J., Marino, M.J. Group III metabotropic glutamote-receptro-mediated modulation of excitatory transmission in rodent substantia nigra pars compacta dopamine neurons. J Pharmacol Exp Ther 2005, 313(3): 1296-304.
190. Vernon, A.C., Zbarsky, V., Datla, K.P., Dexter, D.T., Croucher, M.J. Selective activation of group III metabotropic glutamate receptors by L-(+)-2-amino-4-phosphonobutyric acid protects the nigrostriatal system against 6-hydroxydopamine toxicity in vivo. J Pharmacol Exp Ther 2007, 320(1): 397-409.
191. Battaglia, G., Busceti, C.L., Molinaro, G., Biagioni, F., Traficante, A., Nicoletti, F., Bruno, V. Pharmacological activation of mGlu4 metabotropic glutamate receptors reduces nigrostriatal degeneration in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J Neurosci 2006, 26(27): 7222-9.
192. Cuomo, D., Martella, G., Barabino, E. et al. Metabotropic glutamate receptor subtype 4 selectively modulates both glutamate and GABA transmission in the striatum: Implications for Parkinson's disease treatment. J Neurochem 2009, 109(4): 1096-105.
193. Beurrier, C., Lopez, S., Révy, D. et al. Electrophysiological and behavioral evidence that modulation of metabotropic glutamate receptor 4 with a new agonist reverses experimental parkinsonism. FASEB J 2009, 23(10): 3619-28.
194. Suzuki, G., Kimura, T., Satow, A. et al. Pharmacological characterization of a new, orally active and potent allosteric metabotropic glutamate receptor 1 antagonist, 4-[1-(2-fiuoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N- isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide (FTIDC). J Pharmacol Exp Ther 2007, 321(3): 1144-53.