Metabotropic glutamate receptors as novel targets for anxiety and stress disorders

Nature Reviews Drug Discovery

Volumn 4, Issue 2, 2005, Pages 131-144

  Swanson, Chad J ^a   Bures, Mark ^a   Johnson, Michael P ^a   Linden, Anni Maija ^a   Monn, James A ^a   Schoepp, Darryle D ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 AMINO 1,3 CYCLOPENTANEDICARBOXYLIC ACID; 2 AMINO 2 (2 CARBOXYCYCLOPROPYL) 3 (XANTHEN 9 YL)PROPIONIC ACID; 2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; 4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID A RECEPTOR; 4 CARBOXY 2 METHYLPHENYLGLYCINE; 6 METHYL 2 PHENYLAZO 3 PYRIDINOL; AMPA RECEPTOR ANTAGONIST; BENZODIAZEPINE DERIVATIVE; CORTICOSTERONE; CORTICOTROPIN RELEASING FACTOR ANTAGONIST; DIZOCILPINE; EGLUMETAD; G PROTEIN COUPLED RECEPTOR; GLUTAMATE RECEPTOR; GLUTAMATE RECEPTOR AGONIST; GLUTAMATE RECEPTOR ANTAGONIST; GLUTAMIC ACID; MESSENGER RNA; METABOTROPIC RECEPTOR; METABOTROPIC RECEPTOR AGONIST; METABOTROPIC RECEPTOR ANTAGONIST; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NEUROTRANSMITTER; NORADRENALIN UPTAKE INHIBITOR; PLACEBO; SEROTONIN UPTAKE INHIBITOR; TACHYKININ RECEPTOR ANTAGONIST; UNINDEXED DRUG;

ACUTE STRESS DISORDER; ANXIETY DISORDER; ATAXIA; CENTRAL NERVOUS SYSTEM; CLINICAL TRIAL; DRUG ABUSE; DRUG BIOAVAILABILITY; DRUG POTENCY; DRUG TARGETING; GENE TARGETING; HUMAN; MAMMAL; MEDICAL RESEARCH; MEMORY DISORDER; NERVE CELL EXCITABILITY; NEUROANATOMY; NEUROSCIENCE; NEUROTRANSMISSION; NONHUMAN; POSTSYNAPTIC POTENTIAL; PRESYNAPTIC NERVE; PREVALENCE; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SEDATION; SOMNOLENCE;

ANIMALS; ANXIETY; HUMANS; RECEPTORS, METABOTROPIC GLUTAMATE; STRESS DISORDERS, TRAUMATIC;

EID: 14044258729     PISSN: 14741776     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrd1630     Document Type: Review

References (131)

1. Martin, P. Animal models sensitive to anti-anxiety agents. Acta Psychiatr. Scand. Suppl. 393, 74-80 (1998).
2. Shekhar, A. et al. Summary of a National Institute of Mental Health workshop: developing animal models of anxiety disorders. Psychopharmacology (Berl). 157, 327-339 (2001).
3. Woods, J. H., Katz, J. L. & Winger, G. Benzodiazepines: use, abuse, and consequences. Pharmacol. Rev. 44, 151-347 (1992).
4. Atack, J. R. Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site. Curr. Drug Targets CNS Neurol. Disord. 2, 213-232 (2003).
5. Brunello, N. et al. Noradrenaline in mood and anxiety disorders: basic and clinical studies. Int. Clin. Psychopharmacol. 18, 191-202 (2003).
6. Gorman, J. M. New molecular targets for antianxiety interventions. J. Clin. Psychiatry 64, 28-35 (2003).
7. Kehne, J. & De Lombaert, S. Non-peptidic CRF1 receptor antagonists for the treatment of anxiety, depression and stress disorders. Curr. Drug Targets CNS Neurol. Disord. 1, 467-493 (2002).
8. Holmes, A., Heilig, M., Rupniak, N. M., Steckler, T. & Griebel, G. Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders. Trends Pharmacol. Sci. 24, 580-588 (2003).
9. Vaswani, M., Linda, F. K. & Ramesh, S. Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review. Prog. Neuropsychopharmacol. Biol. Psychiatry 27, 85-102 (2003).
10. Clineschmidt, B. V. Restoration of shock-suppressed behavior by treatment with (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine (MK-801), a substance with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties. Drug Dev. Res. 2, 147-163 (1982).
11. Wiley, J. L. Behavioral pharmacology of N methyl-D-aspartate antagonists: implications for the study and pharmacotherapy of anxiety and schizophrenia. Exp. Clin. Psychopharmacol. 5, 365-374 (1997).
12. Danysz, W., Parsons, C. G., Bresnik, I. & Quack, G. Glutamate in CNS disorders. Drug News Perspec. 8, 261-277 (1996).
13. Parsons, C. G. et al. Modulation of NMDA receptors by glycine - introduction to some basic aspects and recent developments. Amino Acids 14, 207-216 (1998).
14. Schoepp, D. D. Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system. J. Pharmacol. Exp. Ther. 299, 12-20 (2001).
15. Schoepp, D. D. Novel functions for subtypes of metabotropic glutamate receptors. Neurochem. Int. 24, 439-449 (1994).
16. Nakanishi, S. Metabotropic glutamate receptors: synaptic transmission, modulation, and plasticity. Neuron 13, 1031-1037 (1994).
17. Pin, J. P. & Acher, F. The metabotropic glutamate receptors: structure, activation mechanism and pharmacology. Curr. Drug Targets CNS Neurol. Disord. 1, 297-317 (2002).
18. Conn, P. J. & Pin, J. P. Pharmacology and functions of metabotropic glutamate receptors. Annu. Rev. Pharmacol. Toxicol. 37, 205-237 (1997).
19. 2/3 receptor agonists. Ann. NY Acad. Sci. 1003, 309-317 (2003).
20. 2/3 receptor agonist as a novel approach to treat anxiety/stress. Stress 6, 189-197 (2003).
21. Gray, J. A. Precision of the neuropsychopharmacology of anxiety: an inquiry into the functions of the septo-hippocampal system. Behav. Brain Sci. 5, 469-534 (1982).
22. Davis, M. The role of the amygdala in fear and anxiety. Annu. Pev. Neurosci. 15, 353-375 (1992).
23. 2, in the central nervous system of the rat. Neuroscience 53, 1009-1018 (1993).
24. 3) in the rat brain: an in situ hybridization study. J. Comp. Neurol. 335, 252-266 (1993).
25. 3, show unique postsynaptic, presynaptic and glial localizations. Neuroscience 71, 949-976 (1996).
26. 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. 298, 453-460 (2001).
27. Cartmell, J. & Schoepp, D. D. Regulation of neurotransmitter release by metabotropic glutamate receptors. J. Neurochem. 75 889-907 (2000).
28. Anwyl, R. Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Res. Brain Res. Rev. 29, 83-120 (1999).
29. 3 in the mouse CNS: differential location relative to pre- and postsynaptic sites. Neuroscience 106, 481-503 (2001).
30. Helton, D. R., Tizzano, J. P., Monn, J. A., Schoepp, D. D. & Kallman, M. J. Anxiolytic and side-effect profile of LY354740: a potent, highly selective, orally active agonist for group II metabotropic glutamate receptors. J. Pharmacol. Exp. Ther. 284, 651-660 (1998).
31. Walker, D. L. & Davis, M. The role of amygdala glutamate receptors in fear learning, fear-potentiated startle, and extinction. Pharmacol. Biochem. Behav. 71, 379-392 (2002).
32. Campeau, S. & Davis, M. Involvement of subcortical and cortical afferents to the lateral nucleus of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli. J. Neurosci. 15, 2312-2327 (1995).
33. Rainnie, D. G. & Shinnick-Gallagher, P. Trans-ACPD and L-APB presynaptically inhibit excitatory glutamatergic transmission in the basolateral amygdala (BLA). Neurosci. Lett. 139, 87-91 (1992).
34. Pellow, S., Chopin, P., File, S. E. & Briley, M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J. Neurosci. Methods 14, 149-167 (1985).
35. Lister, R. G. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology (Berl). 92, 180-185 (1987).
36. Monn, J. A. 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. 40, 528-537 (1997).
37. Ferris, P., Seward, E. & Dawson, G. R. Interactions between LY354740, a group II metabotropic agonist and the GABA(A)-benzodiazepine receptor complex in the rat elevated plus-maze. J. Psychopharmacol. (Oxf). 15, 76-82 (2001).
38. Engel, J. A., Egbe, P., Liljequist, S. & Soderpalm, B. Effects of amperozide in two animal models of anxiety. Pharmacol. Ther. 64, 429-433 (1989).
39. Nagatani, T. et al. Pharmacological profile of a potential anxiolytic: AP159, a new benzothieno-pyridine derivative. Psychopharmacology (Berl). 104, 432-438 (1991).
40. Assie, M. B., Chopin, P., Stenger, A., Palmier, C. & Briley, M. Neuropharmacology of a new potential anxiolytic compound, F 2692, 1-(3′-trifluoromethylphenyl)-1,4-dihydro-3-amino-4-oxo-6- methylpyridazine. 1. Acute and in vitro effects. Psychopharmacology (Berl). 110, 13-18 (1993).
41. Keim, S. R. & Shekhar A. Chronic GABA dysfunction in the dorsomedial hypothalamus (DMH) of rats results in a panic-prone state that is NMDA and not non-NMDA receptor-mediated. Soc. Neurosci. Abs. 24, 1674 (1998).
42. Shekhar, A. & Keim, S. R. LY354740, a potent group II metabotropic glutamate receptor agonist prevents lactate-induced panic-like response in panic-prone rats. Neuropharmacology 39 1139-1146 (2000).
43. 2/3 receptor agonist LY354740 on the elevated plus maze is associated with the suppression of stress-induced c-Fos in the hippocampus and increases in c-Fos induction in several other stress-sensitive brain regions. Neuropsychopharmacology 29 502-513 (2004).
44. Beck, C. H. M. & Fibiger, H. C. Conditioned fear-induced changes in behavior and in the expression of the immediate early gene c-fos: with and without diazepam pretreatment. J. Neurosci. 15 709-720 (1995).
45. Salminen, O., Lahtinen, S. & Antee, L. Expression of Fos protein in various rat brain areas following acute nicotine and diazepam. Pharmacol. Biochem. Behav. 54, 241-248 (1996).
46. Ryabinin, A. E., Criado, J. R., Henriksen, S. J., Bloom, F. & Wilson, M. C. Differential sensitivity of c-Fos expression in hippocampus and other brain regions to moderate and low doses of alcohol. Mol. Psychiatry 2, 32-43 (1997).
47. Hitzemann, B. & Hitzemann, R. Chlorodiazepoxide-induced expression of c-Fos in the central extended amygdala and other brain regions of the C57BL/6J and DBA/2J inbred mouse strains: relationship to mechanisms of ethanol action. Alcohol. Clin. Exp. Res. 23, 1158-1172 (1999).
48. Sun, N. & Cassell, M. D. Intrinsic GABAergic neurons in the rat central extended amygdala. J. Comp. Neurol. 330, 381-404 (1993).
49. Sun, N., Yi, H. & Cassell, M. D. Evidence for a GABAergic interface between coritcal afferents and brainstem projection neurons in the rat central extended amygdala. J. Comp. Neurol. 340, 43-64 (1994).
50. Veinante, P. & Freund-Mercier, M.-J. Intrinsic and extrinsic connections of the rat central extended amydala: an in vivo electrophysiological study of the central amygdaloid nucleus. Brain Res. 794, 188-198 (1998).
51. Olsen, R. W. Drug interactions at the GABA receptor-ionophore complex. Annu. Rev. Pharmacol. Toxicol. 22, 245-277 (1982).
52. Helton, D. R., Schoepp, D. D., Monn, J. A., Tizzano, J. P. & Kallman, M. J. in Metabotropic Glutamate Receptors in Brain Function (eds. Moroni, F., Nicoletti, F. & Pellegrini-Giampietro, D. E.) 305-314 (Portland, London, 1998).
53. 2 receptors influences cognitive performance in the rodent. Neuropharmacology 46, 907-917 (2004).
54. Moghaddam, B. & Adams, B. W. Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science 281, 1349-1352 (1998).
55. Mohler, H., Fritschy, J. M. & Rudolph, U. A new benzodiazepine pharmacology. J. Pharmacol. Exp. Ther. 300, 2-8 (2002).
56. Low, K. et al. Molecular and neuronal substrate for the selective attenuation of anxiety. Science 290, 131-134 (2000).
57. Nusser, Z., Sieghart, W., Benke, D., Fritschy J. M. & Somogyi, P. Differential synaptic localization of two major γ-aminobutyric acid type A receptor α subunits on hippocampal pyramidal cells. Proc. Natl Acad. Sci. USA 93, 11939-11944 (1996).
58. Fritschy, J. M., Johnson, D. K., Mohler, H. & Rudolph, U. Independent assembly and subcellular targeting of GABA(A)-receptor subtypes demonstrated in mouse hippocampal and olfactory neurons in vivo. Neurosci. Lett. 249, 99-102 (1998).
59. Rudolph, U., Crestani, F. & Mohler, H. GABA(A) receptor subtypes: dissecting their pharmacological functions. Trends Pharmacol. Sci. 22, 188-194 (2001).
60. Barda, D. A. et al. SAR study of a subtype selective allosteric potentiator of metabotropic glutamate 2 receptor, N (4-phenoxyphenyl)-N-(3-pyridinylmethyl)ethanesulfonamide. Bioorg. Med. Chem. Lett. 14, 3099-3102 (2004).
61. 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. 46, 3189-3192 (2003).
62. Johnson, M. P. et al. Biochemical and behavioral characteristics of metabotropic glutamate 2 receptor potentiators. Psychopharmacology (Berl). (in the press).
63. Schaffhauser, H. et al. Pharmacological characterization and identification of amino acids involved in the positive modulation of metabotropic glutamate receptor subtype 2. Mol. Pharmacol. 64, 798-810 (2003).
64. 5 immunoreactivity in rat brain. J. Comp. Neurol. 355, 455-469 (1995).
65. 5, relative to neurotransmitter release sites. J. Chem. Neuroanat. 13, 219-241 (1997).
66. 5 immunolabeling in primate prefrontal cortex. J. Comp. Neurol. 467, 521-535 (2003).
67. 1) and the inositol 1,4,5-trisphosphate receptor in rat brain. J. Neurosci. 13, 2001-2012 (1993).
68. 1 type receptors potentiate transmitter output in the rat cortex. Eur. J. Pharmacol. 347, 189-195 (1998).
69. 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. 20, 7871-7879 (2000).
70. Swanson, C. J., Baker, D. A., Carson, D., Worley, P. F. & Kalivas, P. W. Repeated cocaine administration attenuates group I metabotropic glutamate receptor mediated glutamate release and behavioral activation: a potential role for Homer. J. Neurosci. 21, 9043-9052 (2001).
71. 5α subtypes. Neuropharmacology 34, 887-894 (1995).
72. Chojnacka-Wojcik, E., Tatarczynska, E. & Pilc, A. The anxiolytic-like effect of metabotropic glutamate receptor antagonists after intrahippocampal injection in rats. Eur. J. Pharmacol. 319 153-156 (1997).
73. 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. 14, 3005-3018 (1994).
74. Koch, M. Microinjections of the metabotropic glutamate receptor agonist, trans-(+/-)-1-amino-cyclopentane-1,3-dicarboxylate (trans-ACPD) into the amygdala increase the acoustic startle response of rats. Brain Res. 629, 176-179 (1993).
75. 5 receptor antagonist. Neuropharmacology 38, 1493-1503 (1999).
76. Tatarczynska, E., Klodzinska, A., Kroczka, B., Chojnacka-Wojcik, E. & Pilc, A. The antianxiety-like effects of antagonists of group I and agonists of group II and III metabotropic glutamate receptors after intrahippocampal administration. Psychopharmacology (Berl). 158, 94-99 (2001).
77. 5 receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine on rotarod, locomotor activity and rotational responses in unilateral 6-OHDA-lesioned rats. Eur. J. Pharmacol. 406, 403-410 (2000).
78. 5 receptor antagonist. Br. J. Pharmacol. 132, 1423-1430 (2001).
79. Spooren, W. P. et al. Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine in rodents. J. Pharmacol. Exp. Ther. 295, 1267-1275 (2000).
80. Spooren, W. P., Schoeffer, P., Gasparini, F., Kuhn, R. & Gentsch, C. Pharmacological and endocrinological characterisation of stress-induced hyperthermia in singly housed mice using classical and candidate anxiolytics (LY314582, MPEP and NKP608). Eur. J. Pharmacol. 435, 161-170 (2002).
81. Johnson, M. P., Kelly, G. & Chamberlain, M. Charges in rat serum corticosterone after treatment with metabotropic glutamate receptor agonists or antagonists. J. Neuroendocrinol 13, 670-677 (2001).
82. Brown, M. R. et al. Corticotropin-releasing factor: Effects on the sympathetic nervous system and oxygen consumption. Life Sci. 30, 207-210 (1982).
83. 5 receptor protein in rat hippocampus. Neuropharmacology 39, 1943-1951 (2000).
84. Schulz, B. et al. The metabotropic glutamate receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) blocks fear conditioning in rats. Neuropharmacology 41, 1-7 (2001).
85. Rolls, E. T. A theory of hippocampal function in memory. Hippocampus 6, 601-620 (1996).
86. 5 is required for fear memory formation and long-term potentiation in the lateral amygdala. J. Neurosci. 22, 5219-5229 (2002).
87. Bliss, T. V. & Lomo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. Paris 232, 331-356 (1973).
88. Bear, M. F. & Malenka, R. C. Synaptic plasticity: LTP and LTD. Curr. Opin. Neurobiol. 4, 389-399 (1994).
89. Izumi, Y., Clifford, D. B. & Zorumski, C. F. 2-Amino-3-phosphonopropionate blocks the induction and maintenance of long-term potentiation in rat hippocampal slices. Neurosci. Lett. 122, 187-190 (1991).
90. Behnisch, T. & Reymann, K. G. Co-activation of metabotropic glutamate and N-methyl-D-aspartate receptors is involved in mechanisms of long-term potentiation maintenance in rat hippocampal CA1 neurons. Neuroscience 54, 37-47 (1993).
91. Riedel, G., Casabona, G. & Reymann, K. G. Inhibition of long-term potentiation in the dentate gyrus of freely moving rats by the metabotropic glutamate receptor antagonist MCPG. J. Neurosci. 15 87-98 (1995).
92. Wang, J. & Johnson, K. M. Regulation of striatal cyclic-3′,5′-adenosine monophosphate accumulation and GABA release by glutamate metabotropic and dopamine D1 receptors. J. Pharmacol. Exp. Ther. 275, 877-884 (1995).
93. Wilsch, V. W., Behnisch, T., Jager, T., Reymann, K. G. & Balschun, D. When are class I metabotropic glutamate receptors necessary for long-term potentiation? J. Neurosci. 18, 6071-6080 (1998).
94. 5 agonist CHPG in spinal cord motoneurons. Neuropharmacology 38, 1569-1576 (1999).
95. Nielsen, K. S., Macphail, E. M. & Riedel, G. Class I mGlu receptor antagonist 1-aminoindan-1,5-dicarboxylic acid blocks contextual but not cue conditioning in rats. Eur. J. Pharmacol. 326, 105-108 (1997).
96. Ohno, M. & Watanabe, S. Enhanced N-methyl-D-aspartate function reverses working memory failure induced by blockade of group I metabotropic glutamate receptors in the rat hippocampus. Neurosci. Lett. 240, 37-40 (1998).
97. Semyanov, A. & Kullmann, D. M. Modulation of GABAergic signaling among interneurons by metabotropic glutamate receptors. Neuron 25, 663-672 (2000).
98. Schrader, L. A. & Tasker, J. G. Modulation of multiple potassium currents by metabotropic glutamate receptors in neurons of the hypothalamic supraoptic nucleus. J. Neurophysiol. 78, 3428-3237 (1997).
99. Schrader, L. A. & Tasker, J. G. Presynaptic modulation by metabotropic glutamate receptors of excitatory and inhibitory synaptic inputs to hypothalamic magnocellular neurons. J. Neurophysiol. 77, 527-536 (1997).
100. Tatarczynska, E. et al. Anxiolytic- and antidepressant-like effects of group III metabotropic glutamate agonist (1S,3R,4S)-1-aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-I) in rats. Pol. J. Pharmacol. 54, 707-710 (2002).
101. Chojnacka-Wojcik, E., Tatarczynska, E. & Pilc, A. Anxiolytic-like effects of metabotropic glutamate antagonist (RS)-α-methylserine-O-phosphate in rats. Pol. J. Pharmacol. 48 507-509 (1996).
102. Masugi, M. et al. Metabotropic glutamate receptor subtype 7 ablation causes deficit in fear response and conditioned taste aversion. J. Neurosci. 19, 955-963 (1999).
103. 7. Eur. J. Neurosci. 17, 2409-2417 (2003).
104. 8) receptor. Neuropharmacology 43, 251-259 (2002).
105. Belzung, C. & Griebel, G. Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav. Brain Res. 125 141-149 (2001).
106. Kilbride, J., Huang, L. Q., Rowan, M. J. & Anwyl, R. Presynaptic inhibitory action of the group II metabotropic glutamate receptor agonists, LY354740 and DCG-IV. Eur. J. Pharmacol. 356 149-157 (1998).
107. 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. 292, 76-87 (2000).
108. Neugebauer, V., Chen, P. S. & Willis, W. D. Groups II and III metabotropic glutamate receptors differentially modulate brief and prolonged nociception in primate STT cells. J. Neurophysiol. 84 2998-3009 (2000).
109. 2/3 receptor agonist, LY354740, in the fear-potentiated startle model in rats is mechanistically distinct from diazepam. Pharmacol. Biochem. Behav. 73, 367-374 (2002).
110. 8 receptor knockout mice. Neuropharmacology 45, 473-483 (2003).
111. Walker, D. L., Rattiner, L. M. & Davis, M. Group II metabotropic glutamate receptors within the amygdala regulate fear as assessed with potentiated startle in rats. Behav. Neurosci. 116 1075-1083 (2002).
112. Grillon, C., Cordova, J., Levine, L. R. & Morgan, C. A. Anxiolytic effects of a novel group II metabotropic glutamate receptor agonist (LY354740) in the fear-potentiated startle paradigm in humans. Psychopharmacology (Berl). 168, 446-454 (2003).
113. Klodzinska, A. et al. Potential anti-anxiety, anti-addictive effects of LY 354740, a selective group II glutamate metabotropic receptors agonist in animal models. Neuropharmacology 38, 1831-1839 (1999).
114. 2 agonist, on behaviors suppressed by electric shock, in rats and pigeons. Drug Dev. Res. 47, 37-44 (1999).
115. Moore, N. A., Rees, G. & Monn, J. A. Effects of the group II metabotropic glutamate receptor agonist, LY354740 on schedule-controlled behaviour in rats. Behav. Pharmacol. 10, 319-325 (1999).
116. 2/3 receptor agonist, LY354740, blocks immobilization-induced increases in noradrenaline and dopamine release in the rat medial prefrontal cortex. J. Neurochem. 88, 194-202 (2004).
117. Schoepp, D. D. Case study: utility of metabotropic glutamate agonists in psychiatric illness. 5th World Congress on Stress. Abs 120 (2004).
118. Yamanoi, K. & Ohfune, Y. Synthesis of trans and cis-α-(carboxycyclopropyl)glycines. Novel neuroinhibitory amino acids as L-glutamate analogue. Tetrahedron Lett. 29, 1181-4 (1988).
119. Shimamoto, K., Ishida, M., Shinozaki, H. & Ohfune, Y. Synthesis of four diastereomeric L-2-carboxycyclopropy1) glycines. Conformationally constrained L-glutamate analogues. J. Org. Chem. 56, 4167-4176 (1991).
120. Monn, J. A. 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. 39, 2990-3000 (1996).
121. Acher, F. C. et al. Synthesis and pharmacological characterization of aminocyclopentanetricarboxylic acids: new tools to discriminate between metabotropic glutamate receptor subtypes. J. Med. Chem. 40, 3119-3129 (1997).
122. Kozikowski, A. P. et al. Synthesis and metabotropic glutamate receptor activity of a 2-aminobicyclo[3.2.0] heptane-2,5-dicarboxylic acid, a molecule possessing an extended glutamate conformation. Bioorg. Med. Chem. Lett. 8, 925-930 (1998).
123. Monn, J. A. 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. 42, 1027-1040 (1999).
124. Schoepp, D. D. et al. LY354740 is a potent and highly selective group II metabotropic glutamate receptor agonist in cells expressing human glutamate receptors. Neuropharmacology 36, 1-11 (1997).
125. Malherbe, P. et al. Identification of essential residues involved in the glutamate binding pocket of the group II metabotropic glutamate receptor. Mol. Pharmacol. 60, 944-954 (2001).
126. Kunishima, N. et al. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 407, 971-977 (2000).
127. Varney, M. A. & Suto, C. M. Discovery of subtype-selective metabotropic glutamate receptor ligands using functional HTS assays. Drug Discov. Today 1, 20-26 (2000).
128. Varney, M. A. et al. SIB-1757 and SIB-1893: selective, noncompetitive antagonists of metabotropic glutamate receptor type 5. J. Pharmacol. Exp. Ther. 290, 170-181 (1999).
129. Pagano, A. et al. The non-competitive antagonists 2-methyl-6-(phenylethynyl)pyridine and 7-hydroxyimino-cyclopropan[b]chromen-1a-carboxylic acid ethyl ester interact with overlapping binding pockets in the transmembrane region of group I metabotropic glutamate receptors. J. Biol. Chem. 275, 33750-33758 (2000).
130. Malherbe, P. et al. Mutational analysis and molecular modeling of the binding pocket of the metabotropic glutamate 5 receptor negative modulator 2-methyl-6-(phenylethynyl)-pyridine. Mol. Pharmacol. 64, 823-832 (2003).
131. 3 knockout mice. Psychopharmacol. (in the press).