Molecular pharmacology and therapeutic prospects of metabotropic glutamate receptor allosteric modulators

Basic and Clinical Pharmacology and Toxicology

Volumn 97, Issue 4, 2005, Pages 202-213

  Ritzén, Andreas ^a   Mathiesen, Jesper Mosolff ^a   Thomsen, Christian ^a  

^a H LUNDBECK A S   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

1 AMINO 1,5 INDANDICARBOXYLIC ACID; 2 AMINO 3 (3,4 DICHLOROBENZYLOXY) 6 FLUOROBICYCLO[3.1.0]HEXANE 2,6 DICARBOXYLIC ACID; 2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; 4 AMINO 2 OXABICYCLO[3.1.0]HEXANE 4,6 DICARBOXYLIC ACID; 4 CARBOXY 2 METHYLPHENYLGLYCINE; 4 CARBOXYPHENYLGLYCINE; BAY 36 7620; EGLUMETAD; JNJ 16259685; LY 456066; LY 456236; LY 487379; MEMANTINE; METABOTROPIC RECEPTOR; METABOTROPIC RECEPTOR AGONIST; METABOTROPIC RECEPTOR ANTAGONIST; MGS 0028; PRODRUG; QUISQUALIC ACID; R 214127; TALAGLUMETAD; UNCLASSIFIED DRUG; WO 03093236; WO 0347581;

ALLOSTERISM; ANTICONVULSANT ACTIVITY; CENTRAL NERVOUS SYSTEM; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG STRUCTURE; EPILEPSY; GENERALIZED ANXIETY DISORDER; HUMAN; IC 50; MENTAL DISEASE; NEUROLOGIC DISEASE; NONHUMAN; PANIC; PARKINSON DISEASE; PRIORITY JOURNAL; SCHIZOPHRENIA; SHORT SURVEY; STEREOCHEMISTRY;

ALLOSTERIC REGULATION; ANIMALS; BRAIN DISEASES; EXCITATORY AMINO ACID AGONISTS; EXCITATORY AMINO ACID ANTAGONISTS; HUMANS; MENTAL DISORDERS; RECEPTORS, METABOTROPIC GLUTAMATE;

EID: 26444616159     PISSN: 17427835     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1742-7843.2005.pto_156.x     Document Type: Short Survey

References (71)

1. Annoura, H., A. Fukunaga, M. Uesugi, T. Tatsuoka & Y. Horikawa: A novel class of antagonists for metabotropic glutamate receptors, 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylates. Bioorg. Med. Chem. Lett. 1996, 6, 763-766.
2. Barda, D. A., Z. Q. Wang, T. C. Britton, S. S. Henry, G. E. Jagdmann, D. S. Coleman, M. P. Johnson, S. L. Andis & D. D. Schoepp: SAR study of a subtype selective allosteric potentiator of metabotropic glutamate 2 receptor, N-(4-phenoxyphenyl)-N-(3-pyridinylmethyl)ethanesulfonamide. Bioorg. Med. Chem. Lett. 2004, 14, 3099-3102.
3. Bradley, S. R., M. J. Marino, M. Wittmann, S. T. Rouse, H. Awad, A. I. Levey & P. J. Conn: Activation of group II metabotropic glutamate receptors inhibits synaptic excitation of the substantia Nigra pars reticulata. J. Neurosci. 2000, 20, 3085-3094.
4. Breysse, N., M. Amalric & P. Salin: Metabotropic glutamate 5 receptor blockade alleviates akinesia by normalizing activity of selective basal-ganglia structures in parkinsonian rats. J. Neurosci. 2003, 23, 8302-8309.
5. Bruno, V., G. Battaglia, A. Kingston, M. J. O'Neill, M. V. Catania, R. Di Grezia & F. Nicoletti: Neuroprotective activity of the potent and selective mGlu1a metabotropic glutamate receptor antagonist, (+)-2-methyl-4 carboxyphenylglycine (LY367385): comparison with LY357366, a broader spectrum antagonist with equal affinity for mGlu1a and mGlu5 receptors. Neuropharmacology 1999, 38, 199-207.
6. Bräuner-Osborne, H., J. Egebjerg, E. Ø. Nielsen, U. Madsen & P. Krogsgaard-Larsen: Ligands for glutamate receptors: Design and therapeutic prospects. J. Med. Chem. 2000, 43, 2609-2645.
7. Carroll, F. Y., A. Stolle, P. M. Beart, A. Voerste, I. Brabet, F. Mauler, C. Joly, H. Antonicek, J. Bockaert, T. Muller, J. P. Pin & L. Prezeau: BAY36-7620: A potent non-competitive mGlu1 receptor antagonist with inverse agonist activity. Mol. Pharmacol. 2001, 59, 965-973.
8. Cartmell, J., J. A. Monn & D. D. Schoepp: The metabotropic glutamate 2/3 receptor agonists LY354740 and LY379268 selectively attenuate phencyclidine versus d-amphetamine motor behaviors in rats. J. Pharmacol. Exp. Therap. 1999, 291, 161-170.
9. Chaki, S., R. Yoshikawa, S. Hirota, T. Shimazaki, M. Maeda, N. Kawashima, T. Yoshimizu, A. Yasuhara, K. Sakagami, S. Okuyama, S. Nakanishi & A. Nakazato: MGS0039: a potent and selective group II metabotropic glutamate receptor antagonist with antidepressant-like activity. Neuropharmacology 2004, 46, 457-467.
10. Chen, S. R. & H. L. Pan: Distinct roles of group III metabotropic glutamate receptors in control of nociception and dorsal horn neurons in normal and nerve-injured rats. J. Pharmacol. Exp. Therap. 2005, 312, 120-126.
11. Chiechio, S., A. Copani, D. Melchiorri, A. M. Canudas, M. Storto, M. Calvani, R. Nicolai & F. Nicoletti: Metabotropic receptors as targets for drugs of potential use in the treatment of neuropathic pain. J. Endocrinol. Invest. 2004, 27 Suppl.(6), 171-176.
12. Conn, P. J. & J. P. Pin: Pharmacology and functions of metabotropic glutamate receptors. Annu. Rev. Pharmacol. Toxicol. 1997, 37, 205-237.
13. Cosford, N. D. P., L. Tehrani, J. Roppe, E. Schweiger, N. D. Smith, J. Anderson, L. Bristow, J. Brodkin, X. Jiang, I. McDonald, S. Rao, M. Washburn & M. A. Varney: 3-[(2-Methyl-1,3-thiazol-4-Y1)ethynyl]-pyridine: A potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity. J. Med. Chem. 2003, 46, 204-206.
14. Gasparini, F., K. Lingenhohl, N. Stoehr, P. J. Flor, M. Heinrich, I. Vranesic, M. Biollaz, H. Allgeier, R. Heckendorn, S. Urwyler, M. A. Varney, E. C. Johnson, S. D. Hess, S. P. Rao, A. I. Sacaan, E. M. Santori, G. Velicelebi & R. Kuhn: 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology 1999, 38, 1493-1503.
15. Goudet, C., F. Gaven, J. Kniazeff, C. Vol, J. Liu, M. Cohen-Gonsaud, F. Acher, L. Prezeau & J. P. Pin: Heptahelical domain of metabotropic glutamate receptor 5 behaves like rhodopsin-like receptors. Proc. Natl. Acad. Sci. USA. 2004, 101, 378-383.
16. Grillon, C., J. Cordova, L. R. Levine & C. A. Morgan: Anxiolytic effects of a novel group II metabotropic glutamate receptor agonist (LY354740) in the fear-potentiated startle paradigm in humans. Psychopharmacology (Berl). 2003, 168, 446-454.
17. Heidbreder, C. A., M. Bianchi, L. P. Lacroix, S. Faedo, E. Perdona, R. Remelli, P. Cavanni & F. Crespi: Evidence that the metabotropic glutamate receptor 5 antagonist MPEP may act as an inhibitor of the norepinephrine transporter in vitro and in vivo. Synapse 2003, 50, 269-276.
18. Helton, D. R., J. P. Tizzano, J. A. Monn, D. D. Schoepp & M. J. Kallman: Anxiolytic and side-effect profile of LY354740: a potent, highly selective, orally active agonist for group II metabotropic glutamate receptors. J. Pharmacol. Exp. Therap. 1998, 284, 651-660.
19. Higgins, G. A., T. M. Ballard, J. N. C. Kew, J. Grayson Richards, J. A. Kemp, G. Adam, T. Woltering, S. Nakanishi & V. Mutel: Pharmacological manipulation of mGlu2 receptors influences cognitive performance in the rodent. Neuropharmacology 2004, 46, 907-917.
20. Hu, L.: Prodrugs: Effective solutions for solubility, permeability and targeting challenges. In: IDdB Meeting report. Philadelphia, USA, 2004, June 28-29.
21. Ikonomidou, C. & L. Turski: Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol. 2002, 1, 383-386.
22. Jang, J. H., D. W. Kim, T. Sang Nam, K. Se Paik & J. W. Leem: Peripheral glutamate receptors contribute to mechanical hyperalgesia in a neuropathic pain model of the rat. Neuroscience 2004, 128, 169-176.
23. Johnson, J. T., E. L. Mattiuz, S. H. Chay, J. L. Herman, W. J. Wheeler, K. Kassahun, S. P. Swanson & D. L. Phillips: The disposition, metabolism, and pharmacokinetics of a selective metabotropic glutamate receptor agonist in rats and dogs. Drug Metab. Dispos. 2002, 30, 27-33.
24. Johnson, M. P., M. Baez, G. E. E. Jagdmann, Jr., T. C. Britton, T. H. Large, D. O. Callagaro, J. P. Tizzano, J. A. Monn & D. D. Schoepp: 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.
25. Kew, J. N. C.: Positive and negative allosteric modulation of metabotropic glutamate receptors: emerging therapeutic potential. Pharmacol. Therap. 2004, 104, 233-244.
26. Kinney, G. G., J. A. O'Brien, W. Lemaire, M. Burno, D. J. Bickel, M. K. Clements, T. B. Chen, D. D. Wisnoski, C. W. Lindsley, P. R. Tiller, S. Smith, M. A. Jacobson, C. Sur, M. E. Duggan, D. J. Pettibone, P. H. Conn & D. L. Williams: A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 (mGluR5) has in vivo activity and antipsychotic-like effects in rat behavioral models. J. Pharmacol. Exp. Therap. 2005, in press.
27. Kniazeff, J., A. S. Bessis, D. Maurel, H. Ansanay, L. Prezeau & J. P. Pin: Closed state of both binding domains of homodimeric mGlu receptors is required for full activity. Nat. Struct. Mol. Biol. 2004, 11, 706-713.
28. Knoflach, F., V. Mutel, S. Jolidon, J. N. C. Kew, P. Malherbe, E. Vieira, J. Wichmann & J. A. Kemp: Positive allosteric modulators of metabotropic glutamate 1 receptor: Characterization, mechanism of action, and binding site. Proc. Natl. Acad. Sci. 2001, 98, 13402-13407.
29. Kuang, D., Y. Yao, J. Lam, R. G. Tsushima & D. R. Hampson: Cloning and characterization of a family C orphan G-protein coupled receptor. J. Neurochem. 2005, 93, 383-391.
30. Kunishima, N., Y. Shimada, Y. Tsuji, T. Sato, M. Yamamoto, T. Kumasaka, S. Nakanishi, H. Jingami & K. Morikawa: Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 2000, 407, 971-977.
31. Laruelle, M., L. S. Kegeles & A. Abi-Dargham: Glutamate, dopamine, and schizophrenia: from pathophysiology to treatment. Ann. N.Y. Acad Sci. 2003, 1003, 138-158.
32. 3H]R214127: A novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists. Mol. Pharm. 2003, 63, 1082-1093.
33. Lavreysen, H., R. Wouters, F. Bischoff, S. Nobrega Pereira, X. Langlois, S. Blokland, M. Somers, L. Dillen & A. S. J. Lesage: JNJ16259685, a highly potent, selective and systemically active mGlu1 receptor antagonist. Neuropharmacology 2004, 47, 961-972.
34. Lea, P. M. & A. I. Faden: Modulation of metabotropic glutamate receptors as potential treatment for acute and chronic neurodegenerative disorders. Drug News Perspect. 2003, 16, 513-522.
35. Lindsley, C. W., D. D. Wisnoski, W. H. Leister, J. A. O'Brien, W. Lemaire, D. L. Williams Jr., M. Burno, C. Sur, G. G. Kinney, D. J. Pettibone, P. R. Tiller, S. Smith, M. E. Duggan, G. D. Hartman, P. J. Conn & J. R. Huff: Discovery of positive allosteric modulators for the metabotropic glutamate receptor subtype 5 from a series of N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides that potentiate receptor function in vivo. J. Med. Chem. 2004, 47, 5825-5828.
36. Litschig, S., F. Gasparini, D. Rueegg, N. Stoehr, P. J. Flor, I. Vranesic, L. Prezeau, J. P. Pin, C. Thomsen & R. Kuhn: CPCCOEt, a Noncompetitive Metabotropic Glutamate Receptor 1 Antagonist, Inhibits Receptor Signaling Without Affecting Glutamate Binding. Mol. Pharm. 1999, 55, 453-461.
37. Lorrain, D. S., H. Schaffhauser, U. C. Campbell, C. S. Baccei, L. D. Correa, B. Rowe, D. E. Rodriguez, J. J. Anderson, M. A. Varney, A. B. Pinkerton, J. M. Vernier & L. J. Bristow: Group II mGlu receptor activation suppresses norepinephrine release in the ventral hippocampus and locomotor responses to acute ketamine challenge. Neuropsychopharmacology 2003, 28, 1622-1632.
38. Maj, M., V. Bruno, Z. Dragic, R. Yamamoto, G. Battaglia, W. Inderbitzin, N. Stoehr, T. Stein, F. Gasparini, I. Vranesic, R. Kuhn, F. Nicoletti & P. J. Flor: (-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection. Neuropharmacology 2003, 45, 895-906.
39. Marino, M. J., D. L. Williams Jr., J. A. O'Brien, O. Valenti, T. P. McDonald, M. K. Clements, R. Wang, A. G. DiLella, J. F. Hess, G. G. Kinney & P. J. Conn: Allosteric modulation of group III metabotropic glutamate receptor 4: A potential approach to Parkinson's disease treatment. Proc. Natl. Acad. Sci. 2003, 100, 13668-13673.
40. Mathiesen, J. M., N. Svendsen, H. Bräuner-Osborne, C. Thomsen & M. T. Ramirez: Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP. Brit. J. Pharmacol. 2003, 138, 1026-1030.
41. Micheli, F., R. Di Fabio, P. Cavanni, J. M. Rimland, A. M. Capelli, C. Chiamulera, M. Corsi, C. Corti, D. Donati, A. Feriani, F. Ferraguti, M. Maffeis, A. Missio, E. Ratti, A. Paio, R. Pachera, F. M. Sabbatini, D. G. Trist, A. Ugolini & G. Vitulli: Synthesis and pharmacological characterisation of 2,4-dicarboxy-pyrroles as selective non-competitive mGluR1 antagonists. Bioorg. Med. Chem. 2003a, 11, 171-183.
42. Micheli, F., R. Di Fabio, F. Bordi, P. Cavallini, P. Cavanni, D. Donati, S. Faedo, M. Maffeis, F. M. Sabbatini, G. Tarzia & M. E. Tranquillini: 2,4-Dicarboxy-pyrroles as selective non-competitive mGluR1 antagonists: Further characterization of 3,5-dimethyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester and structure-activity relationships. Bioorg. Med. Chem. Lett. 2003b, 13, 2113-2118.
43. Moldrich, R. X., A. G. Chapman, G. De Sarro & B. S. Meldrum: Glutamate metabotropic receptors as targets for drug therapy in epilepsy. Eur. J. Pharmacol. 2003, 476, 3-16.
44. Mutel, V: Therapeutic potential of non-competitive, subtype-selective metabotropic glutamate receptor ligands. Expert Opinion Ther. Patents 2002, 12, 1845-1852.
45. Nakazato, A., T. Kumagai, K. Sakagami, R. Yoshikawa, Y. Suzuki, S. Chaki, H. Ito, T. Taguchi, S. Nakanishi & S. Okuyama: 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, 4893-4909.
46. Nakazato, A., K. Sakagami, A. Yasuhara, H. Ohta, R. Yoshikawa, M. Itoh, M. Nakamura & S. Chaki: 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, 4570-4587.
47. Neugebauer, V., T. Lucke & H. G. Schaible: Requirement of metabotropic glutamate receptors for the generation of inflammation-evoked hyperexcitability in rat spinal cord neurons. Eur. J. Neurosci. 1994, 6, 1179-1186.
48. Nitsch, R. M., A. Deng, R. J. Wurtman & J. H. Growdon: Metabotropic glutamate receptor subtype mGluR1 alpha stimulates the secretion fo the amyloid beta-protein precursor ectodomain. J. Neurochem. 1997, 69, 704-712.
49. O'Brien, J. A., W. Lemaire, T. B. Chen, R. S. L. Chang, M. A. Jacobson, S. N. Ha, C. W. Lindsley, H. J. Schaffhauser, C. Sur, D. J. Pettibone, P. J. Conn & D. L. Williams Jr.: A family of highly selective allosteric modulators of the metabotropic glutamate receptor subtype 5. Mol. Pharmacol. 2003, 64, 731-740.
50. O'Brien, J. A., L. Wei, M. Wittmann, M. A. Jacobson, S. N. Ha, D. D. Wisnoski, C. W. Lindsley, H. J. Schaffhauser, B. Rowe, C. Sur, M. E. Duggan, D. J. Pettibone, P. J. Conn & D. L. Williams Jr.: A novel selective allosteric modulator potentiates the activity of native metabotropic glutamate receptor subtype 5 in rat forebrain. J. Pharm. Exp. Therap. 2004, 309, 568-577.
51. Parmentier, M. L., L. Prezeau, J. Bockaert & J. P. Pin: A model for the functioning of family 3 GPCRs. Trends Pharmacol. Sci. 2002, 23, 268-274.
52. Parsons, C.: IDdB Meeting report. Soc. Neuroscience Meeting, USA, 2003, November 8-12.
53. Pellegrini-Giampietro, D. E.: The distinct role of mGlu1 receptors in post-ischemic neuronal death. Trends Pharmacol Sci. 2003, 24, 461-70.
54. Pile, A.: LY-354740 Eli Lilly. IDrugs 2003, 6, 66-71.
55. Pin, J.-P., C. De Colle, A.-S. Bessis & F. Archer: New perspectives for the development of selective metabotropic glutamate receptor ligands. Eur. J. Pharmacol. 1999, 375, 277-294.
56. Pin, J. P., T. Galvez & L. Prezeau: Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors. Pharmacol. Therap. 2003, 98, 325-354 (review).
57. Pinkerton, A. B., J. M. Vernier, H. Schaffhauser, B. A. Rowe, U. C. Campbell, D. E. Rodriguez, D. S. Lorrain, C. S. Baccei, L. P. Daggett & L. J. Bristow: Phenyl-tetrazolyl Acetophenones: Discovery of Positive Allosteric Potentiatiors for the Metabotropic Glutamate 2 Receptor. J. Med. Chem. 2004, 47, 4595-4599.
58. Roppe, J. R., B. Wang, D. Huang, L. Tehrani, T. Kamenecka, E. J. Schweiger, J. J. Anderson, J. Brodkin, X. Jiang, M. Cramer, J. Chung, G. Reyes-Manalo, B. Munoz & N. D. R Cosford: 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. 2004b, 14, 3993-3996.
59. Roppe, J., N. D. Smith, D. Huang, L. Tehrani, B. Wang, J. Anderson, J. Brodkin, J. Chung, X. Jiang, C. King, B. Munoz, M. A. Varney, P. Prasit & N. D. P. Cosford: Discovery of novel heteroarylazoles that are metabotropic glutamate subtype 5 receptor antagonists with anxiolytic activity. J. Med. Chem. 2004a, 47, 4645-4648.
60. Sabbatini, F. M. & F. Micheli: Metabotropic glutamate receptors: potential therapeutic applications of recently disclosed new chemical entities. Expert Opinion Ther. Patents 2004, 14, 1593-1604.
61. Schaffhauser, H., B. A. Rowe, S. Morales, L. E. Chavez-Noriega, R. Yin, C. Jachec, S. P. Rao, G. Bain, A. B. Pinkerton, J. M. Vernier, L. J. Bristow, M. A. Varney & L. P. Daggett: Pharmacological characterization and identification of amino acids involved in the positive modulation of metabotropic glutamate receptor subtype 2. Mol. Pharmacol. 2003, 64, 798-810.
62. Schoepp, D. D., D. E. Jane & J. A. Monn: Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology 1999, 38, 1431-1476.
63. Schoepp, D. D., R. A. Wright, L. R. Levine, B. Gaydos & W. Z. Potter: LY354740, an mGlu2/3 receptor agonist as a novel approach to treat anxiety/stress. Stress 2003, 6, 189-197.
64. Sonkusare, S. K., C. L. Kaul & P. Ramarao: Dementia of Alzheimer's disease and other neurodegenerative disorders-memantine, a new hope. Pharmacol. Res. 2005, 51, 1-17.
65. Spooren, W. & F. Gasparini: mGlu5 receptor antagonists: a novel class of anxiolytics? Drug News Perspect. 2004, 17, 251-257.
66. Tong, Q., R. Ouedraogo & A. L. Kirchgessner: Localization and function of group III metabotropic glutamate receptors in rat pancreatic islets. Amer. J. Physiol. Endocrinol. Metab. 2002, 282, E1324-33.
67. Varney, M. A., N. D. Cosford, C. Jachec, S. P. Rao, A. Sacaan, F. F. Lin, L. Bleicher, E. M. Santori, P. J. Flor, H. Allgeier, F. Gasparini, R. Kuhn, S. D. Hess, G. Velicelebi & E. C. Johnson: SIB-1757 and SIB-1893: selective, noncompetitive antagonists of metabotropic glutamate receptor type 5. J. Pharmacol. Exp. Therap. 1999, 290, 170-181.
68. Walker, K., A. Reeve, M. Bowes, J. Winter, G. Wotherspoon, A. Davis, P. Schmid, F. Gasparini, R. Kuhn & L. Urban: mGlu5 receptors and nociceptive function II. mGlu5 receptors functionally expressed on peripheral sensory neurones mediate inflammatory hyperalgesia. Neuropharmacology 2001, 40, 10-19.
69. Wang, B., J. M. Vernier, S. Rao, J. Chung, J. J. Anderson, J. D. Brodkin, X. Jiang, M. F. Gardner, X. Yang & B. Munoz: Discovery of novel modulators of metabotropic glutamate receptor subtype-5. Bioorg. Med. Chem. 2004a, 12, 17-21.
70. Wang, Q., D. M. Walsh, M. J. Rowan, D. J. Selkoe & R. Anwyl: Block of long-term potentiation by naturally secreted and synthetic amyloid b-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5. J. Neurosci. 2004b, 24, 3370-3378.
71. Wellendorph, P., K. B. Hansen, A. Balsgaard, J. R. Greenwood, J. Egebjerg & H. Brauner-Osborne: Deorphanization of GPRC6A: A promiscuous L-alpha-amino acid receptor with preference for basic amino acids. Mol. Pharmacol. 2005, 67: 589-597.